Gene Symbol: ERP44
Description: endoplasmic reticulum protein 44
Alias: PDIA10, TXNDC4, endoplasmic reticulum resident protein 44, ER protein 44, endoplasmic reticulum resident protein 44 kDa, protein disulfide isomerase family A, member 10, thioredoxin domain containing 4 (endoplasmic reticulum), thioredoxin domain-containing protein 4
Species: human
Products:     ERP44

Top Publications

  1. Fraldi A, Zito E, Annunziata F, Lombardi A, Cozzolino M, Monti M, et al. Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44. Hum Mol Genet. 2008;17:2610-21 pubmed publisher
    ..Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles ..
  2. Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, et al. Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J. 2003;22:5015-22 pubmed
    ..Here we show that ERp44 mediates Ero1alpha ER localization through the formation of reversible mixed disulfides...
  3. Vavassori S, Cortini M, Masui S, Sannino S, Anelli T, Caserta I, et al. A pH-regulated quality control cycle for surveillance of secretory protein assembly. Mol Cell. 2013;50:783-92 pubmed publisher
    ..Here we unveil how ERp44 cycles between cisGolgi and ER in a pH-regulated manner, patrolling assembly of disulfide-linked oligomers such as ..
  4. Otsu M, Bertoli G, Fagioli C, Guerini Rocco E, Nerini Molteni S, Ruffato E, et al. Dynamic retention of Ero1alpha and Ero1beta in the endoplasmic reticulum by interactions with PDI and ERp44. Antioxid Redox Signal. 2006;8:274-82 pubmed
    ..Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way...
  5. Anelli T, Ceppi S, Bergamelli L, Cortini M, Masciarelli S, Valetti C, et al. Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis. EMBO J. 2007;26:4177-88 pubmed
    ..How is efficiency of IgM secretion coupled to fidelity? We show here that ERp44, a soluble protein involved in thiol-mediated retention, interacts with ERGIC-53...
  6. Mariappan M, Radhakrishnan K, Dierks T, Schmidt B, von Figura K. ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum. J Biol Chem. 2008;283:6375-83 pubmed publisher
    ..Thereby formylglycine is generated, which is essential for sulfatase activity. Here we show that ERp44 interacts with FGE forming heterodimeric and, to a lesser extent, also heterotetrameric and octameric complexes, ..
  7. Wang L, Wang L, Vavassori S, Li S, Ke H, Anelli T, et al. Crystal structure of human ERp44 shows a dynamic functional modulation by its carboxy-terminal tail. EMBO Rep. 2008;9:642-7 pubmed publisher
    b>ERp44 mediates thiol-dependent retention in the early secretory pathway, forming mixed disulphides with substrate proteins through its conserved CRFS motif. Here, we present its crystal structure at a resolution of 2.6 A...
  8. Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, et al. ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 2002;21:835-44 pubmed
    ..Here, we characterize a novel ER resident protein (ERp44), which contains a thioredoxin domain with a CRFS motif and is induced during ER stress...
  9. Grilz Seger G, Druml T, Neuditschko M, Dobretsberger M, Horna M, Brem G. High-resolution population structure and runs of homozygosity reveal the genetic architecture of complex traits in the Lipizzan horse. BMC Genomics. 2019;20:174 pubmed publisher
    ..Around the STX17 gene (causative for greying), we identified a ROH island harbouring the genes NR4A3, STX17, ERP44 and INVS...

More Information


  1. Watanabe S, Amagai Y, Sannino S, Tempio T, Anelli T, Harayama M, et al. Zinc regulates ERp44-dependent protein quality control in the early secretory pathway. Nat Commun. 2019;10:603 pubmed publisher
    ..Here, we show that Zn2+ binds with high affinity to the pH-sensitive chaperone ERp44, modulating its localization and ability to retrieve clients like Ero1α and ERAP1 to the endoplasmic reticulum (..
  2. Fu Y, Zhang B, Mu T. LMAN1 (ERGIC-53) promotes trafficking of neuroreceptors. Biochem Biophys Res Commun. 2019;511:356-362 pubmed publisher
    ..LMAN1 knockout regulates the ER proteostasis network by upregulating ERP44 without changing calnexin levels...
  3. Liyanage D, Omeka W, Lee J. Molecular characterization, host defense mechanisms, and functional analysis of ERp44 from big-belly seahorse: A novel member of the teleost thioredoxin family present in the endoplasmic reticulum. Comp Biochem Physiol B Biochem Mol Biol. 2019;232:31-41 pubmed publisher
    b>Endoplasmic reticulum resident protein 44 (ERp44) is a protein disulfide isomerase (PDI) and a member of thioredoxin family, which is involved in several functions such as oxidative folding and polymerization of molecules, carrier ..
  4. Hendershot L, Feige M, Buchner J. Acidification activates ERp44--a molecular litmus test for protein assembly. Mol Cell. 2013;50:779-81 pubmed publisher
    ..2013) show that a pH-induced conformational change in the quality control protein ERp44 allows retrieval of secretory proteins that contain free thiols via a disulfide linkage from postendoplasmic ..
  5. Jin D, Sun J, Huang J, Yu X, Yu A, He Y, et al. Peroxisome proliferator-activated receptor γ enhances adiponectin secretion via up-regulating DsbA-L expression. Mol Cell Endocrinol. 2015;411:97-104 pubmed publisher differentiated 3T3-L1 cells, PPARγ knockdown resulted in decreased expression of Adiponectin, DsbA-L and ERp44. DsbA-L expression increased after PPARγ agonist treatment and decreased upon treatment with PPARγ ..
  6. Tomicek N, Lancaster T, Korzick D. Increased estrogen receptor β in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats. Gend Med. 2011;8:325-33 pubmed publisher
    ..05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09)...
  7. Yang K, Gotzmann J, Kuny S, Huang H, Sauve Y, Chan C. Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes. J Endocrinol. 2016;229:343-56 pubmed publisher
    ..accumulation of proinsulin and C-peptide inside islets), and endoplasmic reticulum (ER) chaperone protein ERp44 was upregulated in insulin-producing β-cells...
  8. Pang X, Zhang Y, Shi X, Li D, Han J. ERp44 depletion exacerbates ER stress and aggravates diabetic nephropathy in db/db mice. Biochem Biophys Res Commun. 2018;504:921-926 pubmed publisher
    ..b>ERp44, an ER resident chaperone protein, has been implicated in the modulation of ER stress, however, its role and ..
  9. Achari A, Jain S. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017;18: pubmed publisher
    ..reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently ..
  10. Tsuchiya Y, Saito M, Kadokura H, Miyazaki J, Tashiro F, Imagawa Y, et al. IRE1-XBP1 pathway regulates oxidative proinsulin folding in pancreatic β cells. J Cell Biol. 2018;217:1287-1301 pubmed publisher
    ..folding of proinsulin along with decreased expression of five protein disulfide isomerases (PDIs): PDI, PDIR, P5, ERp44, and ERp46...
  11. Cho J, Jeon Y, Park S, Shin J, Lee T, Jung S, et al. Multifunctional effects of honokiol as an anti-inflammatory and anti-cancer drug in human oral squamous cancer cells and xenograft. Biomaterials. 2015;53:274-84 pubmed publisher
    ..cell lines, HN22 and HSC4, through the regulation of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum resident protein 44 (ERp44)...
  12. He Y, Lu L, Wei X, Jin D, Qian T, Yu A, et al. The multimerization and secretion of adiponectin are regulated by TNF-alpha. Endocrine. 2016;51:456-68 pubmed publisher
    ..TNF-α remarkably suppressed the expression of the ER-resident chaperone proteins ERO1-La, DsbA-L, and ERp44. Overexpression of the transcription factor PPARγ antagonized the suppressive effect of TNF-α on ERO1-La and ..
  13. Dai X, Liu X, Meng Q. Segmental expression and C-terminal labeling of protein ERp44 through protein trans-splicing. Protein Expr Purif. 2015;112:29-36 pubmed publisher
    b>Endoplasmic reticulum resident protein 44 (ERp44) is a member of the protein disulfide isomerase family and functions in oxidative protein folding in the endoplasmic reticulum...
  14. Anelli T, Sannino S, Sitia R. Proteostasis and "redoxtasis" in the secretory pathway: Tales of tails from ERp44 and immunoglobulins. Free Radic Biol Med. 2015;83:323-30 pubmed publisher
    ..despite the massive fluxes of cargo proteins traversing the pathway? Here we describe recent findings on how ERp44, a multifunctional chaperone of the secretory pathway, can modulate these processes integrating protein QC, ..
  15. Wanders D, Graff E, White B, Judd R. Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice. PLoS ONE. 2013;8:e71285 pubmed publisher
    ..Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion)...
  16. Wang D, Abbasi C, El Rass S, Li J, Dawood F, Naito K, et al. Endoplasmic reticulum resident protein 44 (ERp44) deficiency in mice and zebrafish leads to cardiac developmental and functional defects. J Am Heart Assoc. 2014;3:e001018 pubmed publisher
    Endoplasmic reticulum (ER) resident protein 44 (ERp44) is a member of the protein disulfide isomerase family, is induced during ER stress, and may be involved in regulating Ca(2+) homeostasis...
  17. Hisatsune C, Ebisui E, Usui M, Ogawa N, Suzuki A, Mataga N, et al. ERp44 Exerts Redox-Dependent Control of Blood Pressure at the ER. Mol Cell. 2015;58:1015-27 pubmed publisher
    ..Here, we show that angiotensin II is regulated by ERp44, a factor involved in disulfide bond formation in the ER...
  18. Zhang J, Zhu Q, Wang X, Yu J, Chen X, Wang J, et al. Secretory kinase Fam20C tunes endoplasmic reticulum redox state via phosphorylation of Ero1α. EMBO J. 2018;37: pubmed publisher the ER, is phosphorylated by Fam20C in the Golgi apparatus and retrograde-transported to the ER mediated by ERp44. The phosphorylation of Ser145 greatly enhances Ero1α oxidase activity and is critical for maintaining ER redox ..
  19. Olivares García V, Torre Villalvazo I, Velázquez Villegas L, Alemán G, Lara N, López Romero P, et al. Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats. Nutr Diabetes. 2015;5:e184 pubmed publisher
    ..Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARÎ..
  20. Liu Y, Liu C, Jiang C, Wang S, Yang Q, Jiang D, et al. C-reactive protein inhibits high-molecular-weight adiponectin expression in 3T3-L1 adipocytes via PI3K/Akt pathway. Biochem Biophys Res Commun. 2016;472:19-25 pubmed publisher
    ..Furthermore, CRP decreased the HMW/total adiponectin ration and reduced adiponectin assembly by increasing ERp44, and decreasing Ero1-α and DsbA-L. CRP activated pAkt, the downstream of PI3K...
  21. Winship A, Sorby K, Correia J, Rainczuk A, Yap J, Dimitriadis E. Interleukin-11 up-regulates endoplasmic reticulum stress induced target, PDIA4 in human first trimester placenta and in vivo in mice. Placenta. 2017;53:92-100 pubmed publisher
    ..IL11 stimulated ERP44, but not GRP94, or PDI...
  22. Png E, Alisjahbana B, Sahiratmadja E, Marzuki S, Nelwan R, Balabanova Y, et al. A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians. BMC Med Genet. 2012;13:5 pubmed publisher
    ..or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may ..
  23. Chang Y, Wu Y, Liu W, Ji G. Knockdown of ERp44 leads to apoptosis via activation of ER stress in HeLa cells. Biochem Biophys Res Commun. 2015;463:606-11 pubmed publisher
    b>ERp44, an endoplasmic reticulum (ER) resident protein, regulates intracellular Ca(2+) release and involves in the maturation of many proteins in mammalian cells...
  24. Hampe L, Radjainia M, Xu C, Harris P, Bashiri G, Goldstone D, et al. Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44. J Biol Chem. 2015;290:18111-23 pubmed publisher
    ..The endoplasmic reticulum (ER) chaperone ERp44 retains adiponectin in the early secretory compartment and tightly controls the oxidative state of Cys(39) and the ..
  25. Watanabe S, Harayama M, Kanemura S, Sitia R, Inaba K. Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface. Proc Natl Acad Sci U S A. 2017;114:E3224-E3232 pubmed publisher
    b>ERp44 retrieves some endoplasmic reticulum (ER)-resident enzymes and immature oligomers of secretory proteins from the Golgi...
  26. Yang K, Li D, Wang X, Liang J, Sitia R, Wang C, et al. Crystal Structure of the ERp44-Peroxiredoxin 4 Complex Reveals the Molecular Mechanisms of Thiol-Mediated Protein Retention. Structure. 2016;24:1755-1765 pubmed publisher
    b>ERp44 controls the localization and transport of diverse proteins in the early secretory pathway. The mechanisms that allow client recognition and the source of the oxidative power for forming intermolecular disulfides are as yet unknown...
  27. Higo T, Hattori M, Nakamura T, Natsume T, Michikawa T, Mikoshiba K. Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44. Cell. 2005;120:85-98 pubmed
    ..In this study, we found that ERp44, an ER lumenal protein of the thioredoxin family, directly interacts with the third lumenal loop of IP(3)R type 1 (..
  28. Galligan J, Petersen D. The human protein disulfide isomerase gene family. Hum Genomics. 2012;6:6 pubmed publisher
    ..Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR. ..
  29. Hampe L, Xu C, Harris P, Chen J, Liu M, Middleditch M, et al. Synthetic peptides designed to modulate adiponectin assembly improve obesity-related metabolic disorders. Br J Pharmacol. 2017;174:4478-4492 pubmed publisher
    ..functionally important higher molecular weight (HMW) forms, controlled by the endoplasmic reticulum protein 44 (ERp44)...
  30. Zhao L, Bracken M, Dewan A. Genome-wide association study of pre-eclampsia detects novel maternal single nucleotide polymorphisms and copy-number variants in subsets of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort. Ann Hum Genet. 2013;77:277-87 pubmed publisher
    ..Several variants were suggestively replicated in SOPHIA. The discovered SNPs and copy-number variable regions present interesting candidate genetic variants for pre-eclampsia that warrant further replication and investigation. ..
  31. Holbrook L, Watkins N, Simmonds A, Jones C, Ouwehand W, Gibbins J. Platelets release novel thiol isomerase enzymes which are recruited to the cell surface following activation. Br J Haematol. 2010;148:627-37 pubmed publisher
    ..of five additional thiol isomerases in human and mouse platelets and megakaryocytes, namely; ERp57, ERp72, ERp44, ERp29 and TMX3...
  32. O Neill E, Brock C, von Kriegsheim A, Pearce A, Dwek R, Watson S, et al. Towards complete analysis of the platelet proteome. Proteomics. 2002;2:288-305 pubmed
    ..This study contributes to a more thorough and holistic understanding of platelet biology, helping to build the basis for future identification of new drug targets and therapeutic strategies. ..
  33. Zou Y, Jiang Z, Yu X, Zhang Y, Sun M, Wang W, et al. MiR-101 regulates apoptosis of trophoblast HTR-8/SVneo cells by targeting endoplasmic reticulum (ER) protein 44 during preeclampsia. J Hum Hypertens. 2014;28:610-6 pubmed publisher
    ..association between miR-101 and apoptosis of human trophoblast cells mediated by endoplasmic reticulum protein 44 (ERp44) in preeclampsia (PE), we explored the expression of miR-101 in PE placentas (n=30) compared with normotensive ..
  34. Li Y, Hadden C, Singh P, Mercado C, Murphy P, Dajani N, et al. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake. Proc Natl Acad Sci U S A. 2014;111:E5697-705 pubmed publisher
    ..We previously reported that an endoplasmic reticulum chaperone, ERp44, binds to Cys200 and Cys209 residues of SERT to build a disulfide bond...
  35. Wise R, Duhachek Muggy S, Qi Y, Zolkiewski M, Zolkiewska A. Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells. Breast Cancer Res Treat. 2016;157:241-252 pubmed publisher
    ..Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells ..
  36. Alloza I, Baxter A, Chen Q, Matthiesen R, Vandenbroeck K. Celecoxib inhibits interleukin-12 alphabeta and beta2 folding and secretion by a novel COX2-independent mechanism involving chaperones of the endoplasmic reticulum. Mol Pharmacol. 2006;69:1579-87 pubmed
    ..reticulum-resident chaperone involved in the retention of misfolded cargo proteins while blocking interaction with ERp44. Our findings reveal a previously undescribed effect of celecoxib on oligomer protein folding and assembly in the ..
  37. Sannino S, Anelli T, Cortini M, Masui S, Degano M, Fagioli C, et al. Progressive quality control of secretory proteins in the early secretory compartment by ERp44. J Cell Sci. 2014;127:4260-9 pubmed publisher
    b>ERp44 is a pH-regulated chaperone of the secretory pathway...
  38. Kakihana T, Araki K, Vavassori S, Iemura S, Cortini M, Fagioli C, et al. Dynamic regulation of Ero1? and peroxiredoxin 4 localization in the secretory pathway. J Biol Chem. 2013;288:29586-94 pubmed publisher
    ..Their secretion is prevented by sequential interactions with PDI and ERp44, two resident proteins of the ESC-bearing KDEL-like motifs...