ATP2C2
ATPase Secretory Pathway Ca2+ Transporting 2
Gene Information Card
| Symbol | ATP2C2 |
|---|---|
| Full Name | ATPase Secretory Pathway Ca2+ Transporting 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q24.1 |
| NCBI Gene ID | 9914 ncbi.nlm.nih.gov/gene/9914 |
| Ensembl ID | ENSG00000161960 |
| UniProt ID | O75185 |
| OMIM ID | 613082 |
| HGNC ID | 13225 |
| Aliases | SPCA2, hSPCA2, ATP2C2 |
Description
ATP2C2 encodes secretory pathway Ca2+/Mn2+-ATPase 2 (SPCA2), a P-type ATPase that transports calcium and manganese ions from the cytosol into the Golgi apparatus and secretory vesicles. It plays a critical role in maintaining cellular calcium homeostasis, protein glycosylation, and secretory pathway function. SPCA2 is highly expressed in secretory tissues and has been implicated in breast cancer and Hailey-Hailey disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hailey-Hailey disease (HHD) | Loss-of-function mutations in ATP2C2 impair Golgi calcium uptake, leading to defective desmosome assembly and acantholysis in keratinocytes. | OMIM #613082; ClinVar |
| Breast cancer | Overexpression of SPCA2 promotes store-independent calcium entry and activates NFAT signaling, contributing to tumorigenesis. | PubMed; COSMIC |
| Keratinocyte disorders | Dysregulation of calcium homeostasis due to ATP2C2 mutations disrupts epidermal barrier function. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Mammary gland | 12.5 | Medium |
| Salivary gland | 10.8 | Medium |
| Pancreas | 8.2 | Medium |
| Skin | 6.1 | Low |
| Brain | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| HaCaT (keratinocyte) | 9.8 | Moderate expression |
| HEK293 | 7.5 | Moderate expression |
| HeLa | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.742C>T (p.Arg248*) | Nonsense | Rare | Loss of function; associated with Hailey-Hailey disease |
| c.1790G>A (p.Arg597His) | Missense | Rare | Impaired calcium transport activity |
| c.2041C>T (p.Arg681Cys) | Missense | Rare | Reduced ATPase activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish calcium transport activity, leading to Hailey-Hailey disease.
Gain of Function (GOF)
Overexpression in breast cancer cells enhances store-independent calcium entry and NFAT activation.
Dominant Negative (DN)
Not reported for ATP2C2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Golgi-to-ER retrograde transport (Reactome: R-HSA-6811434)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
Protein Summary
SPCA2 is a 946-amino acid P-type ATPase with 10 transmembrane domains, localized to the Golgi and post-Golgi vesicles. It pumps Ca2+ and Mn2+ into the secretory pathway, essential for proper protein glycosylation and sorting. Its C-terminal domain interacts with STIM1 to mediate store-independent calcium entry. Mutations cause Hailey-Hailey disease, while overexpression is linked to breast cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP2C2 Knockout HEK293 Cell Line | EDJ-KQ6815 | Human | 9914 | Details Get a Quote |
| ATP2C2 Knockout HCT 116 Cell Line | EDJ-KQ31337 | Human | 9914 | Details Get a Quote |
| ATP2C2 Knockout HeLa Cell Line | EDJ-KQ55277 | Human | 9914 | Details Get a Quote |
| ATP2C2 Knockout A-549 Cell Line | EDJ-KQ63758 | Human | 9914 | Details Get a Quote |
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