Gene Symbol: CDC50A
Description: transmembrane protein 30A
Alias: C6orf67, CDC50A, cell cycle control protein 50A, P4-ATPase flippase complex beta subunit TMEM30A
Species: human
Products:     CDC50A

Top Publications

  1. Folmer D, Mok K, de Wee S, Duijst S, Hiralall J, Seppen J, et al. Cellular localization and biochemical analysis of mammalian CDC50A, a glycosylated β-subunit for P4 ATPases. J Histochem Cytochem. 2012;60:205-18 pubmed publisher
    ..This study analyzed the tissue distribution and cellular localization of CDC50A, the most abundant and ubiquitously expressed CDC50 homologue in the mouse...
  2. Yang F, Huang Y, Chen X, Liu L, Liao D, Zhang H, et al. Deletion of a flippase subunit Tmem30a in hematopoietic cells impairs mouse fetal liver erythropoiesis. Haematologica. 2019;: pubmed publisher
    ..Our findings demonstrate that Tmem30a plays a critical role in erythropoiesis by regulating the EPOR signaling pathway through the formation of membrane rafts in erythroid cells. ..
  3. Zhang S, Liu W, Yang Y, Sun K, Li S, Xu H, et al. Tmem30a Deficiency in endothelial cells impairs cell proliferation and angiogenesis. J Cell Sci. 2019;: pubmed publisher
    ..Mechanistically, deletion of TMEM30A caused reduced EC proliferation by inhibiting VEGF-induced signaling. Our findings reveal essential roles of TMEM30A in angiogenesis, and providing a potential therapeutic target. ..
  4. Yang Y, Sun K, Liu W, Zhang L, Peng K, Zhang S, et al. Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje cells. Cell Death Dis. 2018;9:899 pubmed publisher
    ..Taken together, our data demonstrate an essential role of Tmem30a in the cerebellum PCs. ..
  5. Gao H, Yang Z, Wang X, Qian P, Hong R, Chen X, et al. ISP1-Anchored Polarization of GC?/CDC50A Complex Initiates Malaria Ookinete Gliding Motility. Curr Biol. 2018;28:2763-2776.e6 pubmed publisher
    ..b>CDC50A, a co-factor of P4-ATPase, binds to and stabilizes GC? during ookinete development...
  6. Tsuchiya M, Hara Y, Okuda M, Itoh K, Nishioka R, Shiomi A, et al. Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation. Nat Commun. 2018;9:2049 pubmed publisher
    ..the inward translocation of phosphatidylserine, which is driven by the phospholipid flippase complex of ATP11A and CDC50A, is required for PIEZO1 activation...
  7. Naito T, Takatsu H, Miyano R, Takada N, Nakayama K, Shin H. Phospholipid Flippase ATP10A Translocates Phosphatidylcholine and Is Involved in Plasma Membrane Dynamics. J Biol Chem. 2015;290:15004-17 pubmed publisher
    ..5 P4-ATPases to the plasma membrane (ATP10A and ATP10D) and late endosomes (ATP10B) requires an interaction with CDC50A. Moreover, exogenous expression of ATP10A, but not its ATPase-deficient mutant ATP10A(E203Q), dramatically ..
  8. Wang J, Molday L, Hii T, Coleman J, Wen T, Andersen J, et al. Proteomic Analysis and Functional Characterization of P4-ATPase Phospholipid Flippases from Murine Tissues. Sci Rep. 2018;8:10795 pubmed publisher
    ..Most P4-ATPases associate with one of three accessory subunit isoforms known as CDC50A (TMEM30A), CDC50B (TMEM30B), and CDC50C (TMEM30C)...
  9. Braggio E, Van Wier S, Ojha J, McPhail E, Asmann Y, Egan J, et al. Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas. Clin Cancer Res. 2015;21:3986-94 pubmed publisher
    ..In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas. ..

More Information


  1. Vestergaard A, Mikkelsen S, Coleman J, Molday R, Vilsen B, Andersen J. Specific mutations in mammalian P4-ATPase ATP8A2 catalytic subunit entail differential glycosylation of the accessory CDC50A subunit. FEBS Lett. 2015;589:3908-14 pubmed publisher
    ..alanine screening of the mammalian flippase ATP8A2 catalytic subunit, five mutations stand out by leading to reduced glycosylation of the accessory subunit CDC50A. These mutations may disturb the interaction between the subunits.
  2. Ansari I, Longacre M, Paulusma C, Stoker S, Kendrick M, MacDonald M. Characterization of P4 ATPase Phospholipid Translocases (Flippases) in Human and Rat Pancreatic Beta Cells: THEIR GENE SILENCING INHIBITS INSULIN SECRETION. J Biol Chem. 2015;290:23110-23 pubmed publisher
    ..b>CDC50A is a protein that forms a heterodimer with P4 ATPases to enhance their translocase catalytic activity...
  3. Li N, Yang Y, Liang C, Qiu Q, Pan C, Li M, et al. Tmem30a Plays Critical Roles in Ensuring the Survival of Hematopoietic Cells and Leukemia Cells in Mice. Am J Pathol. 2018;188:1457-1468 pubmed publisher
    ..Our results also revealed that targeting Tmem30a signaling had therapeutic utility in BCR/ABL1-induced chronic myeloid leukemia. ..
  4. Segawa K, Kurata S, Nagata S. Human Type IV P-type ATPases That Work as Plasma Membrane Phospholipid Flippases and Their Regulation by Caspase and Calcium. J Biol Chem. 2016;291:762-72 pubmed publisher
    ..As with ATP11C, ATP8A2 and ATP11A localized to the plasma membrane in a CDC50A-dependent manner...
  5. Chalat M, Moleschi K, Molday R. C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity. Mol Biol Cell. 2017;28:452-462 pubmed publisher
    ..the role of the C-terminus of ATP8A2 in its expression, subcellular localization, interaction with its subunit CDC50A, and function as a phosphatidylserine flippase...
  6. Johnson K, Reynard L, Loughlin J. Functional characterisation of the osteoarthritis susceptibility locus at chromosome 6q14.1 marked by the polymorphism rs9350591. BMC Med Genet. 2015;16:81 pubmed publisher
    ..As implied by the dynamic patterns of gene expression throughout chondrogenesis, the association signal marked by rs9350591 could instead be exerting its effects during joint development. ..
  7. Segawa K, Kurata S, Nagata S. The CDC50A extracellular domain is required for forming a functional complex with and chaperoning phospholipid flippases to the plasma membrane. J Biol Chem. 2018;293:2172-2182 pubmed publisher
    ..membrane is ATP11C, a type IV P-type ATPase (P4-ATPase) that forms a heterocomplex with the transmembrane protein CDC50A. However, the structural features in CDC50A that support the function of ATP11C and other P4-ATPases have not been ..
  8. Coleman J, Molday R. Critical role of the beta-subunit CDC50A in the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2. J Biol Chem. 2011;286:17205-16 pubmed publisher
    ..Here, we show by mass spectrometry and Western blotting using newly generated anti-CDC50A antibodies that CDC50A is associated with ATP8A2 purified from photoreceptor membranes...
  9. Liu L, Zhang L, Zhang L, Yang F, Zhu X, Lu Z, et al. Hepatic Tmem30a Deficiency Causes Intrahepatic Cholestasis by Impairing Expression and Localization of Bile Salt Transporters. Am J Pathol. 2017;187:2775-2787 pubmed publisher
    ..Therefore, TMEM30A may be a novel genetic determinant of intrahepatic cholestasis. ..
  10. van der Mark V, Ghiboub M, Marsman C, Zhao J, van Dijk R, Hiralall J, et al. Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4. Cell Mol Life Sci. 2017;74:715-730 pubmed publisher
    ..Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced ..
  11. Takada N, Takatsu H, Miyano R, Nakayama K, Shin H. ATP11C mutation is responsible for the defect in phosphatidylserine uptake in UPS-1 cells. J Lipid Res. 2015;56:2151-7 pubmed publisher
    ..By contrast, the level of ATP11A, another PS-flipping P4-ATPase at the plasma membrane, or CDC50A, which is essential for delivery of most P4-ATPases to the plasma membrane, was not affected in UPS-1 cells...
  12. Segawa K, Kurata S, Yanagihashi Y, Brummelkamp T, Matsuda F, Nagata S. Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure. Science. 2014;344:1164-8 pubmed publisher
    ..Using a haploid genetic screen in human cells, we found that ATP11C (adenosine triphosphatase type 11C) and CDC50A (cell division cycle protein 50A) are required for aminophospholipid translocation from the outer to the inner ..
  13. Folmer D, van der Mark V, Ho Mok K, Oude Elferink R, Paulusma C. Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1. Hepatology. 2009;50:1597-605 pubmed publisher
    ..ATP8B1 interacts with CDC50A, which is required for endoplasmic reticulum exit and plasma membrane localization...
  14. Wang J, Wang Q, Lu D, Zhou F, Wang D, Feng R, et al. A biosystems approach to identify the molecular signaling mechanisms of TMEM30A during tumor migration. PLoS ONE. 2017;12:e0179900 pubmed publisher
  15. van der Mark V, de Waart D, Ho Mok K, Tabbers M, Voogt H, Oude Elferink R, et al. The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface expression of the apical sodium-dependent bile acid transporter (SLC10A2/ASBT) in intestinal Caco-2 cells. Biochim Biophys Acta. 2014;1842:2378-86 pubmed publisher
    ..Moreover, we show that endogenous ATP8B1 exists in a functional heterodimer with transmembrane protein 30A (CDC50A) in Caco-2 cells...
  16. Chen R, Brady E, McIntyre T. Human TMEM30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells. J Immunol. 2011;186:3215-25 pubmed publisher
    ..Variation in this mechanism could limit sensitivity to short chain choline phospholipids such as Edelfosine, PAF, and proapoptotic phospholipids. ..
  17. van der Velden L, Wichers C, van Breevoort A, Coleman J, Molday R, Berger R, et al. Heteromeric interactions required for abundance and subcellular localization of human CDC50 proteins and class 1 P4-ATPases. J Biol Chem. 2010;285:40088-96 pubmed publisher
    ..ATP8B1 and ATP8B2 co-immunoprecipitated with CDC50A and CDC50B, whereas ATP8B4, ATP8A1, and ATP8A2 associated only with CDC50A...
  18. Paulusma C, Folmer D, Ho Mok K, de Waart D, Hilarius P, Verhoeven A, et al. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity. Hepatology. 2008;47:268-78 pubmed
    ..We have studied the role of two human members of this family, CDC50A and CDC50B, in the routing and activity of ATP8B1...
  19. Takatsu H, Baba K, Shima T, Umino H, Kato U, Umeda M, et al. ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes to the trans-Golgi network in a CDC50 protein-independent manner. J Biol Chem. 2011;286:38159-67 pubmed publisher
    ..ATP10A, ATP10B, and ATP10D) and class 6 (ATP11A, ATP11B, and ATP11C) P4-ATPases require CDC50 proteins, primarily CDC50A, for their exit from the endoplasmic reticulum (ER) and final subcellular localization...
  20. Katoh Y, Katoh M. Identification and characterization of CDC50A, CDC50B and CDC50C genes in silico. Oncol Rep. 2004;12:939-43 pubmed
    ..b>C6orf67 and FLJ33850 were representative human CDC50A and CDC50B cDNAs, respectively...
  21. Zhang L, Yang Y, Li S, Zhang S, Zhu X, Tai Z, et al. Loss of Tmem30a leads to photoreceptor degeneration. Sci Rep. 2017;7:9296 pubmed publisher
    ..Our data demonstrated novel essential roles of Tmem30a in the retina. ..
  22. Kato U, Inadome H, Yamamoto M, Emoto K, Kobayashi T, Umeda M. Role for phospholipid flippase complex of ATP8A1 and CDC50A proteins in cell migration. J Biol Chem. 2013;288:4922-34 pubmed publisher
    ..ovary (CHO) cells, at least eight members of P4-ATPases were identified, but only a single CDC50 family protein, CDC50A, was expressed. We demonstrated that CDC50A associated with and recruited P4-ATPase ATP8A1 to the plasma membrane...
  23. Muñoz Martínez F, Torres C, Castanys S, Gamarro F. CDC50A plays a key role in the uptake of the anticancer drug perifosine in human carcinoma cells. Biochem Pharmacol. 2010;80:793-800 pubmed publisher
    ..Over-expression and knockdown of the human beta subunit CDC50A in KB cells enhanced and decreased, respectively, the uptake of both fluorescent aminophospholipid analogues and ..