ATP2C1
Function
ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (PubMed:12707275, PubMed:16192278, PubMed:20439740, PubMed:21187401, PubMed:30923126). Within a catalytic cycle, acquires Ca(2+) or Mn(2+) 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 Ca(2+) 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:14632183, PubMed:20439740). Responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity (PubMed:10615129, PubMed:14632183, PubMed:20439740). Participates in Ca(2+) and Mn(2+) 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 Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity (PubMed:21187401).
Involvement in disease
Hailey-Hailey disease
HHD
An autosomal dominant cutaneous disorder characterized by erythema, skin blisters and erosions, and suprabasal acantholysis. Blisters and erosions most often affect the neck, armpits, skin folds, groin and genitals.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
Tissue Specificity
Found in most tissues except colon, thymus, spleen and leukocytes (PubMed:15831496). Expressed in keratinocytes (at protein level) (PubMed:14632183, PubMed:15831496).
Cellular localization
- Golgi apparatus
- trans-Golgi network membrane
- Multi-pass membrane protein
- Golgi apparatus
- Golgi stack membrane
- Multi-pass membrane protein
- 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.
Alternative names
KIAA1347, PMR1L, HUSSY-28, ATP2C1, Calcium-transporting ATPase type 2C member 1, ATPase 2C1, ATP-dependent Ca(2+) pump PMR1, Ca(2+)/Mn(2+)-ATPase 2C1, Secretory pathway Ca(2+)-transporting ATPase type 1, SPCA1