ATP2C1
- Known as:
- ATP2C1
- Catalog number:
- 002178A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATP2C1
Related genes to: ATP2C1
- Gene:
- ATP2C1 NIH gene
- Name:
- ATPase secretory pathway Ca2+ transporting 1
- Previous symbol:
- BCPM
- Synonyms:
- KIAA1347, ATP2C1A, PMR1, SPCA1
- Chromosome:
- 3q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-19
- Date modifiied:
- 2016-10-05
Related products to: ATP2C1
Related articles to: ATP2C1
- The secretory pathway Ca-ATPase, SPCA1 (gene name ), is a Golgi-localized calcium pump defective in the autosomal dominant cutaneous disorder known as Hailey-Hailey disease (HHD). Although clinically well characterized by suprabasal acantholysis and intertriginous blistering of the skin, the mechanistic underpinnings of the disease are still unclear. Here we use CRISPR/Cas9-mediated single- and biallelic knockouts in immortalized human N/TERT keratinocytes to show that SPCA1 is required for dynamic reorganization of actin cytoskeleton in keratinocyte spreading, which is the primary mechanism driving skin reepithelialization. We identify an insulin-activated PI3K-AKT-Rac1 signaling pathway required for lamellipodia formation and keratinocyte spreading, defective in SPCA1 knockout cell lines. Our findings may explain the poor wound healing and impaired keratinocyte migration observed in HHD and may be relevant to the observed effect of insulin on wound healing, including diabetic wounds and burns, reported for nearly a century. Transgenic expression of hSPCA1 or treatment with CDN1163, a small molecule Ca-ATPase agonist, restored defective phenotypes in the HHD model, paving the way for future therapeutic approaches to treat this disorder. Keratinocytes spread and change shape dynamically to maintain skin integrity and facilitate the rapid repair of the skin barrier after injury. Defects in these processes are characteristic of Hailey-Hailey disease (HHD), an ulcerative skin disorder caused by mutations in the Golgi Ca-ATPase SPCA1. By developing new keratinocyte HHD models, we uncover a role for SPCA1 in an insulin-activated signaling pathway that drives lamellipodia formation and keratinocyte spreading, linking Ca regulation to actin cytoskeleton reorganization. - Source: PubMed
Publication date: 2026/08/17
Gupta RubyChinchole AkashPaul Ngozi PSarkar Mrinal KGudjonsson Johann EVerma AjayRao Rajini - Hailey-Hailey disease (HHD) is an autosomal dominantly inherited blistering dermatosis caused by mutations in the gene, which encodes the human secretory pathway Ca⁺/Mn⁺ ATPase protein (hSPCA1). - Source: PubMed
Publication date: 2026/07/13
Ye YouxingDeng BaoqingLiang Yanhua - Hailey-Hailey disease (HHD) is a rare autosomal dominant blistering disorder caused by mutations in the ATP2C1 gene, which impair keratinocyte adhesion through disrupted calcium signaling. While traditionally considered a structural defect, recent studies suggest that Th2-mediated inflammation may exacerbate disease pathology. Interleukin (IL)-4 and IL-13, central mediators of type 2 inflammation, have been implicated in barrier dysfunction in other dermatoses, yet their role in HHD remains poorly defined. - Source: PubMed
Publication date: 2026/07/06
Gaumond Simonetta ISoto VictoriaAbujamra Beatriz AbdoRongioletti FrancoMcGrath John AJozic IvanRomanelli Paolo - - Source: PubMed
Debeuf Marie-Eline P Hvan Veen Fauve C A PSpätjens DiedeKimman Merel Lvan Geel MichelSteijlen Peter MGostynski Antoni HVerstraeten Valerie L R M - Hailey-Hailey disease (HHD) is a genetic skin blistering disorder lacking approved treatments despite linkage to variants 25 years ago. Since knockout mice did not replicate HHD, we ablated in human keratinocytes or chemically inhibited its encoded Golgi calcium pump SPCA1. In organotypic epidermis, SPCA1 deficiency or inhibition reproduced HHD pathology, disrupting desmosomal cadherins and severing cell-cell junctions, termed acantholysis. RNA sequencing of heterozygous cells identified dysregulation of actin and Rho GTPases along with EGF receptor signaling as potential pathogenic drivers. Accordingly, SPCA1-depleted organotypic epidermis and HHD biopsies exhibited cortical actin disorganization and hyper-phosphorylation of the Rho kinase (ROCK) target, myosin light chain. Rho activation was sufficient to induce acantholysis, while ROCK inhibition partially restored heterozygous keratinocyte cohesion. A fluorescent biosensor demonstrated ERK hyper-activation in heterozygous cells along with desmosomal cadherin mis-localization. Importantly, treating SPCA1-deficient keratinocyte sheets with MEK and ROCK inhibitors together fully restored their integrity. Our results show HHD blistering is driven by desmosome and cortical actin dysfunction that was mitigated by targeting MEK and ROCK with repurposed drugs, offering a viable treatment strategy. Moreover, our model provides a blueprint for replicating genetic epidermal disorders to delineate pathogenic mechanisms and vet therapeutics for other orphan skin diseases. - Source: PubMed
Publication date: 2026/05/23
Ayers Jessica LParihar ArtiTiwaa AfuaAravind AkshataMartin Michael CPence KugaTam Crystal JSutter NizhoniSkruber KristenSarkar Mrinal KGudjonsson Johann ESimpson Cory L