ATP10A

Last update 08 May 2025

Basic Info

Synonyms

Aminophospholipid translocase VA, ATP10A, ATP10C

+ [7]

Introduction

Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane (PubMed:25947375, PubMed:29599178, PubMed:30530492). Initiates inward plasma membrane bending and recruitment of Bin/amphiphysin/Rvs (BAR) domain-containing proteins involved in membrane tubulation and cell trafficking (PubMed:29599178). Facilitates ITGB1/beta1 integrin endocytosis, delaying cell adhesion and cell spreading on extracellular matrix (PubMed:25947375, PubMed:29599178). Has low flippase activity toward glucosylceramide (GlcCer) (PubMed:30530492).

100 Clinical Results associated with ATP10A

100 Translational Medicine associated with ATP10A

0 Patents (Medical) associated with ATP10A

Literatures (Medical) associated with ATP10A

18 Sep 2024·Biochemical Journal

Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane

Article

Author: Shigetomi, Ryo ; Takatsu, Hiroyuki ; Shin, Hye-Won ; Nakayama, Kazuhisa ; Muranaka, Yumeka ; Hamamoto, Asuka ; Iwasaki, Yugo

Phosphatidylinositol is a precursor of various phosphoinositides, which play crucial roles in intracellular signaling and membrane dynamics and have impact on diverse aspects of cell physiology. Phosphoinositide synthesis and turnover occur in the cytoplasmic leaflet of the organellar and plasma membranes. P4-ATPases (lipid flippases) are responsible for translocating membrane lipids from the exoplasmic (luminal) to the cytoplasmic leaflet, thereby regulating membrane asymmetry. However, the mechanism underlying phosphatidylinositol translocation across cellular membranes remains elusive. Here, we discovered that the phosphatidylcholine flippases ATP8B1, ATP8B2, and ATP10A can also translocate phosphatidylinositol at the plasma membrane. To explore the function of these phosphatidylinositol flippases, we used cells depleted of CDC50A, a protein necessary for P4-ATPase function and ATP8B1 and ATP8B2, which express in HeLa cells. Upon activation of the Gq-coupled receptor, depletion of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was accelerated in CDC50A knockout (KO) and ATP8B1/8B2 double KO cells compared with control cells, suggesting a decrease in PtdIns(4,5)P2 levels within the plasma membrane of the KO cells upon stimulation. These findings highlight the important role of P4-ATPases in maintaining phosphoinositide homeostasis and suggest a mechanism for asymmetry of phosphatidylinositol in the cytoplasmic leaflet of the plasma membrane.

15 Sep 2024·International Journal of Cancer

Methylation markers for anal cancer screening: A repeated cross‐sectional analysis of people living with HIV, 2015–2016

Article

Author: Schouten, Jeffrey ; Hawes, Stephen E. ; Winer, Rachel L. ; Barnabas, Ruanne V. ; Lin, John ; Feng, Qinghua ; Stankiewicz Karita, Helen C. ; Vasavada, Anjali ; Wasserheit, Judith

AbstractPeople living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high‐grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low‐grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high‐resolution anoscopy (HRA) in Seattle, Washington, 2015–2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01–1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08–1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01–1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08–1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

03 Jan 2024·Journal of Animal Science

Effect of genotyping density on the detection of runs of homozygosity and heterozygosity in cattle

Article

Author: Macciotta, Nicolò Pietro Paolo ; Falchi, Laura ; Mastrangelo, Salvatore ; Hidalgo, Jorge ; Cesarani, Alberto ; Criscione, Andrea ; Garcia, Andre

AbstractRuns of homozygosity (ROHom) are contiguous stretches of homozygous regions of the genome. In contrast, runs of heterozygosity (ROHet) are heterozygosity-rich regions. The detection of these two types of genomic regions (ROHom and ROHet) is influenced by the parameters involved in their identification and the number of available single-nucleotide polymorphisms (SNPs). The present study aimed to test the effect of chip density in detecting ROHom and ROHet in the Italian Simmental cattle breed. A sample of 897 animals were genotyped at low density (50k SNP; 397 individuals), medium density (140k SNP; 348 individuals), or high density (800k SNP; 152 individuals). The number of ROHom and ROHet per animal (nROHom and nROHet, respectively) and their average length were calculated. ROHom or ROHet shared by more than one animal and the number of times a particular SNP was inside a run were also computed (SNPROHom and SNPROHet). As the chip density increased, the nROHom increased, whereas their average length decreased. In contrast, the nROHet decreased and the average length increased as the chip density increased. The most repeated ROHom harbored no genes, whereas in the most repeated ROHet four genes (SNRPN, SNURF, UBE3A, and ATP10A) previously associated with reproductive traits were found. Across the 3 datasets, 31 SNP, located on Bos taurus autosome (BTA) 6, and 37 SNP (located on BTA21) exceeded the 99th percentile in the distribution of the SNPROHom and SNPROHet, respectively. The genomic region on BTA6 mapped the SLIT2, PACRGL, and KCNIP4 genes, whereas 19 and 18 genes were mapped on BTA16 and BTA21, respectively. Interestingly, most of genes found through the ROHet analysis were previously reported to be related to health, reproduction, and fitness traits. The results of the present study confirm that the detection of ROHom is more reliable when the chip density increases, whereas the ROHet trend seems to be the opposite. Genes and quantitative trait loci (QTL) mapped in the highlighted regions confirm that ROHet can be due to balancing selection, thus related to fitness traits, health, and reproduction, whereas ROHom are mainly involved in production traits. The results of the present study strengthened the usefulness of these parameters in analyzing the genomes of livestock and their biological meaning.

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ATP10A

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