| Name | pepsinogen 4, group I (pepsinogen A) |
| Description | This gene encodes a protein precursor of the digestive enzyme pepsin, a member of the peptidase A1 family of endopeptidases. The encoded precursor is secreted by gastric chief cells and undergoes autocatalytic cleavage in acidic conditions to form the active enzyme, which functions in the digestion of dietary proteins. This gene is found in a cluster of related genes on chromosome 11, each of which encodes one of multiple pepsinogens. Pepsinogen levels in serum may serve as a biomarker for atrophic gastritis and gastric cancer. [provided by RefSeq, Jul 2015] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPMCA4 (ATP2B4) is a plasma membrane Ca²⁺‐ATPase that plays a vital role in maintaining Ca²⁺ homeostasis in reproductive cells. In sperm, PMCA4 is highly enriched and precisely localized to the principal piece of the tail, where it prevents Ca²⁺ overload and is essential for the hyperactivated motility required for male fertility. Its ablation or pharmacological inhibition leads to impaired sperm hyperactivation, Ca²⁺ dysregulation (including mitochondrial condensation and ATP deficits), and subsequently male infertility. In addition, specialized splice variants—such as the epididymally secreted PMCA4a—are transferred to maturing sperm via exosomes, further augmenting their Ca²⁺ clearance capacity. Androgen receptor activation has been shown to upregulate PMCA4 expression during testis development, reinforcing its role in spermatogenesis. Moreover, interactions with regulatory molecules like CASK and JAM‐A fine tune its activity and establish links with nitric oxide synthases that impact NO production in the sperm."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cardiovascular and smooth muscle context, PMCA4 serves not only as an effector of Ca²⁺ extrusion but also as a critical scaffold. In cardiac myocytes, PMCA4 orchestrates microdomains by tethering neuronal nitric oxide synthase (nNOS), thereby modulating local cyclic nucleotide signals (cGMP and cAMP) and ultimately adjusting contractile function and β-adrenergic responsiveness. In vascular, bladder, and intestinal smooth muscles, its activity influences contractility and relaxation kinetics; when overexpressed or disrupted, PMCA4 can affect arterial tone and blood pressure. Its proper function also depends on localization within specialized membrane microdomains such as caveolae, and it additionally influences fibroblast paracrine signaling and vascular smooth muscle cell proliferation through cell cycle regulatory mediators."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in excitable tissues, PMCA4 contributes to Ca²⁺ regulation in diverse epithelial and neuronal contexts. In the retina, its preferential expression in synaptic layers supports rapid Ca²⁺ clearance essential for visual signal modulation, while in the kidney and intestinal epithelia, PMCA4 appears to perform a housekeeping role in transepithelial Ca²⁺ transport—even though the primary transporter in some instances is PMCA1. Alternative splicing events further dictate PMCA4’s subcellular targeting in polarized cells, enabling localized control of Ca²⁺ dynamics. Conversely, in lymphoid cells such as B cells, PMCA4 is barely detectable, with PMCA1 assuming the prominent Ca²⁺ extrusion function. In neural stem cells, however, upregulation of PMCA4 enhances resistance to oxidative stress, and during enamel maturation, diminished PMCA4 expression is associated with disrupted pH regulation, underscoring its broader significance in Ca²⁺-dependent developmental processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gbolahan W Okunade, Marian L Miller, Gail J Pyne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M404628200"}], "href": "https://doi.org/10.1074/jbc.M404628200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15178683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15178683"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kai Schuh, Elizabeth J Cartwright, Eriks Jankevics, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M312599200"}], "href": "https://doi.org/10.1074/jbc.M312599200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15078889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15078889"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Amal A Al-Dossary, Emanuel E Strehler, Patricia A Martin-Deleon "}, {"type": "b", "children": [{"type": "t", "text": "Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0080181"}], "href": "https://doi.org/10.1371/journal.pone.0080181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24244642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24244642"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ramkrishna Patel, Amal A Al-Dossary, Deborah L Stabley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane Ca2+-ATPase 4 in murine epididymis: secretion of splice variants in the luminal fluid and a role in sperm maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.113.108712"}], "href": "https://doi.org/10.1095/biolreprod.113.108712"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23699388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23699388"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rolands G Aravindan, Victor P Fomin, Ulhas P Naik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.24000"}], "href": "https://doi.org/10.1002/jcp.24000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22020416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22020416"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rui Sun, Hui Liang, Huan Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PMCA4 gene expression is regulated by the androgen receptor in the mouse testis during spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2020.11791"}], "href": "https://doi.org/10.3892/mmr.2020.11791"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33355366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33355366"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nicholas Stafford, Min Zi, Florence Baudoin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PMCA4 inhibition does not affect cardiac remodelling following myocardial infarction, but may reduce susceptibility to arrhythmia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-81170-2"}], "href": "https://doi.org/10.1038/s41598-021-81170-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33452399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33452399"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sarah Withers, Elizabeth J Cartwright, Ludwig Neyses "}, {"type": "b", "children": [{"type": "t", "text": "Sperm phenotype of mice carrying a gene deletion for the plasma membrane calcium/calmodulin dependent ATPase 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2005.12.028"}], "href": "https://doi.org/10.1016/j.mce.2005.12.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16442703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16442703"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kristine E Olli, Kun Li, Deni S Galileo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane calcium ATPase 4 (PMCA4) co-ordinates calcium and nitric oxide signaling in regulating murine sperm functional activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.25882"}], "href": "https://doi.org/10.1002/jcp.25882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28247940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28247940"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Tamer M A Mohamed, Delvac Oceandy, Min Zi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane calcium pump (PMCA4)-neuronal nitric-oxide synthase complex regulates cardiac contractility through modulation of a compartmentalized cyclic nucleotide microdomain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.290411"}], "href": "https://doi.org/10.1074/jbc.M111.290411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21965681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21965681"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Tamer M A Mohamed, Riham Abou-Leisa, Nicholas Stafford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11074"}], "href": "https://doi.org/10.1038/ncomms11074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27020607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27020607"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kai Schuh, Thomas Quaschning, Sebastian Knauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of vascular tone in animals overexpressing the sarcolemmal calcium pump."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307606200"}], "href": "https://doi.org/10.1074/jbc.M307606200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12900399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12900399"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Tamer M A Mohamed, Delvac Oceandy, Sukhpal Prehar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific role of neuronal nitric-oxide synthase when tethered to the plasma membrane calcium pump in regulating the beta-adrenergic signal in the myocardium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M809112200"}], "href": "https://doi.org/10.1074/jbc.M809112200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19278978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19278978"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Li Liu, Yukisato Ishida, Gbolahan Okunade, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of plasma membrane Ca2+-ATPase in contraction-relaxation processes of the bladder: evidence from PMCA gene-ablated mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00440.2005"}], "href": "https://doi.org/10.1152/ajpcell.00440.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16291816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16291816"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Ahmed F El-Yazbi, Woo Jung Cho, Richard Schulz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcium extrusion by plasma membrane calcium pump is impaired in caveolin-1 knockout mouse small intestine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2008.06.098"}], "href": "https://doi.org/10.1016/j.ejphar.2008.06.098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18634779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18634779"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Talat Afroze, Ge Yang, Amir Khoshbin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcium efflux activity of plasma membrane Ca2+ ATPase-4 (PMCA4) mediates cell cycle progression in vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.533638"}], "href": "https://doi.org/10.1074/jbc.M113.533638"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24448801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24448801"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sophronia Lewis, Robert Little, Florence Baudoin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acute inhibition of PMCA4, but not global ablation, reduces blood pressure and arterial contractility via a nNOS-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13371"}], "href": "https://doi.org/10.1111/jcmm.13371"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29193716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29193716"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Kerstin Abshagen, Bastian Degenhardt, Marie Liebig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver-specific Repin1 deficiency impairs transient hepatic steatosis in liver regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-35325-3"}], "href": "https://doi.org/10.1038/s41598-018-35325-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30442920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30442920"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ellen P M van Loon, Robert Little, Sukhpal Prehar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcium Extrusion Pump PMCA4: A New Player in Renal Calcium Handling?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0153483"}], "href": "https://doi.org/10.1371/journal.pone.0153483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27101128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27101128"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "David Krizaj, Steven J Demarco, Juliette Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell-specific expression of plasma membrane calcium ATPase isoforms in retinal neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.10281"}], "href": "https://doi.org/10.1002/cne.10281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12209837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12209837"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "R Todd Alexander, Megan R Beggs, Reza Zamani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00651.2014"}], "href": "https://doi.org/10.1152/ajprenal.00651.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26180241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26180241"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Géza Antalffy, Amy S Mauer, Katalin Pászty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane calcium pump (PMCA) isoform 4 is targeted to the apical membrane by the w-splice insert from PMCA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Calcium (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ceca.2011.12.010"}], "href": "https://doi.org/10.1016/j.ceca.2011.12.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22252018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22252018"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "C E Tye, R Sharma, C E Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered ion-responsive gene expression in Mmp20 null mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dent Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0022034510384625"}], "href": "https://doi.org/10.1177/0022034510384625"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20929715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20929715"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Mark Korthals, Laura Tech, Kristina Langnaese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " homeostasis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.202048654"}], "href": "https://doi.org/10.1002/eji.202048654"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33098669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33098669"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Shaochen Nie, Wenhao Zhang, Xin Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Screening of Haploid Neural Stem Cells Reveals that Nfkbia and Atp2b4 are Key Regulators of Oxidative Stress in Neural Precursors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Sci (Weinh) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/advs.202309292"}], "href": "https://doi.org/10.1002/advs.202309292"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38666459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38666459"}]}]}]}
|
| Proteins | PEPA4_HUMAN |
| NCBI Gene ID | 643847 |
| API | |
| Download Associations | |
| Predicted Functions |
 |
| Co-expressed Genes |
|
| Expression in Tissues and Cell Lines |
|
PGA4 has 1,314 functional associations with biological entities spanning 7 categories (molecular profile, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 55 datasets.
Click the + buttons to view associations for PGA4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of PGA4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of PGA4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of PGA4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with PGA4 gene from the CellMarker Gene-Cell Type Associations dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of PGA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing PGA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing PGA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with PGA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with PGA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with PGA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with PGA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with PGA4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with PGA4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with PGA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of PGA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of PGA4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing PGA4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of PGA4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of PGA4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving PGA4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving PGA4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving PGA4 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing PGA4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing PGA4 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing PGA4 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by PGA4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by PGA4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by PGA4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of PGA4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of PGA4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of PGA4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of PGA4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of PGA4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of PGA4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for PGA4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of PGA4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of PGA4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways 2026 | pathways involving PGA4 protein from the KEGG Pathways 2026 dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of PGA4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain PGA4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of PGA4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving PGA4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving PGA4 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2024 | pathways involving PGA4 protein from the Reactome Pathways 2024 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of PGA4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of PGA4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of PGA4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of PGA4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of PGA4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of PGA4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of PGA4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of PGA4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with PGA4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with PGA4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving PGA4 protein from the WikiPathways Pathways 2024 dataset. | |
