ATP2C1

The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ATPase Secretory Pathway Ca2+ Transporting 1

ATP-driven pump that supplies the Golgi apparatus with Ca2+ and Mn2+ ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:16192278, PubMed:30923126, PubMed:21187401, PubMed:12707275, PubMed:20439740).
Within a catalytic cycle, acquires Ca2+ or Mn2+ ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:16192278, PubMed:16332677, PubMed:30923126).
Plays a primary role in the maintenance of Ca2+ homeostasis in the trans-Golgi compartment with a functional impact on Golgi and post-Golgi protein sorting as well as a structural impact on cisternae morphology (PubMed:20439740, PubMed:14632183).
Responsible for loading the Golgi stores with Ca2+ ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity (PubMed:14632183, PubMed:10615129, PubMed:20439740).
Participates in Ca2+ and Mn2+ ions uptake into the Golgi store of hippocampal neurons and regulates protein trafficking required for neural polarity (By similarity).
May also play a role in the maintenance of Ca2+ and Mn2+ homeostasis and signaling in the cytosol while preventing cytotoxicity (PubMed:21187401).

Actin cytoskeleton reorganization Source: UniProtKB
Calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules Source: UniProtKB
Calcium ion transmembrane transport Source: GO_Central
Calcium ion transport Source: UniProtKB
Cellular calcium ion homeostasis Source: UniProtKB
Cellular manganese ion homeostasis Source: UniProtKB
Epidermis development Source: UniProtKB
Golgi calcium ion homeostasis Source: UniProtKB
Golgi calcium ion transport Source: UniProtKB
Ion transmembrane transport Source: Reactome
Manganese ion transport Source: UniProtKB
Positive regulation of Golgi to plasma membrane protein transport Source: UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Trans-Golgi network membrane organization Source: UniProtKB

Trans-Golgi network membrane; Golgi stack membrane. During neuron differentiation, shifts from juxtanuclear Golgi position to multiple Golgi structures distributed over the neural soma with a predominance in the apical dendritic trunk.

Hailey-Hailey disease (HHD): Autosomal dominant disorder characterized by persistent blisters and suprabasal cell separation (acantholysis) of the epidermis, due to impaired keratinocyte adhesion. Patients lacking all isoforms except isoform 2 have HHD.

Cytoplasmic: 1-70 aa
Helical: 71-91 aa
Lumenal: 92-104 aa
Helical: 105-123 aa
Cytoplasmic: 124-262 aa
Helical: 263-282 aa
Lumenal: 283-294 aa
Helical: 295-312 aa
Cytoplasmic: 313-699 aa
Helical: 700-719 aa
Lumenal: 720-729 aa
Helical: 730-750 aa
Cytoplasmic: 751-770 aa
Helical: 771-793 aa
Lumenal: 794-808 aa
Helical: 809-828 aa
Cytoplasmic: 829-841 aa
Helical: 842-860 aa
Lumenal: 861-875 aa
Helical: 876-896 aa
Cytoplasmic: 897-919 aa