Gene Symbol: hspa5
Description: heat shock protein 5
Alias: cb865, fb60h09, fi36d04, wu:fb60h09, wu:fi36d04, zgc:55994, zgc:77606, 78 kDa glucose-regulated protein, bip, glucose-regulated protein, 78kDa, heat shock 70kDa protein 5 (glucose-regulated protein)
Species: zebrafish
Products:     hspa5

Top Publications

  1. Passeri M, Cinaroglu A, Gao C, Sadler K. Hepatic steatosis in response to acute alcohol exposure in zebrafish requires sterol regulatory element binding protein activation. Hepatology. 2009;49:443-52 pubmed publisher
    ..EtOH) for 32 hours achieves approximately 80 mM intracellular EtOH and up-regulation of hepatic cyp2e1, sod, and bip, indicating that EtOH is metabolized and provokes oxidant stress...
  2. Niu X, Gao C, Jan Lo L, Luo Y, Meng C, Hong J, et al. Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish. Dev Biol. 2012;367:197-207 pubmed publisher
    ..Our data provide the first direct genetic evidence that COPII function is essential for the organogenesis of the digestive system...
  3. Pyati U, Gjini E, Carbonneau S, Lee J, Guo F, Jette C, et al. p63 mediates an apoptotic response to pharmacological and disease-related ER stress in the developing epidermis. Dev Cell. 2011;21:492-505 pubmed publisher
  4. Thakur P, Stuckenholz C, Rivera M, Davison J, Yao J, Amsterdam A, et al. Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish. Hepatology. 2011;54:452-62 pubmed publisher
    ..ER stress markers, including atf6, hspa5, calr, and xbp1, are selectively up-regulated in the mutant liver...
  5. Howarth D, Vacaru A, Tsedensodnom O, Mormone E, Nieto N, Costantini L, et al. Alcohol disrupts endoplasmic reticulum function and protein secretion in hepatocytes. Alcohol Clin Exp Res. 2012;36:14-23 pubmed publisher
    ..Mobility of the major ER chaperone, BIP, was monitored in cells by fluorescence recovery after photobleaching (FRAP)...
  6. Blanco Sanchez B, Clément A, Fierro J, Washbourne P, Westerfield M. Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis. Dis Model Mech. 2014;7:547-59 pubmed publisher
    ..ER stress, thus, contributes to sensory hair cell loss and provides a new target to explore for protective therapies for USH. ..
  7. Falisse E, Voisin A, Silvestre F. Impacts of triclosan exposure on zebrafish early-life stage: Toxicity and acclimation mechanisms. Aquat Toxicol. 2017;189:97-107 pubmed publisher
    ..This research highlighted oxidative stress and neurotoxicity as major toxicity mechanisms of TCS during development. ..
  8. Moussavi Nik S, Newman M, Wilson L, Ebrahimie E, Wells S, Musgrave I, et al. Alzheimer's disease-related peptide PS2V plays ancient, conserved roles in suppression of the unfolded protein response under hypoxia and stimulation of γ-secretase activity. Hum Mol Genet. 2015;24:3662-78 pubmed publisher
    ..Our data support a model in which chronic hypoxia in aged brains promotes excessive Notch signalling and accumulation of Aβ that contribute to AD pathogenesis. ..
  9. Sousa M, Silva A, Malhão F, Rocha M, Rocha E, Urbatzka R. Reproductive hormones affect follicular cells and ooplasm of Stage I and II oocytes in zebrafish. Reprod Fertil Dev. 2016;28:1945-1952 pubmed publisher
    ..B and E) and resident proteins of the endoplasmic reticulum (calnexin and 78-kDa glucose-regulated protein (grp78/bip))...

More Information


  1. Cao J, Navis A, Cox B, Dickson A, Gemberling M, Karra R, et al. Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration. Development. 2016;143:232-43 pubmed publisher
    ..Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration. ..
  2. Christen V, Capelle M, Fent K. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish. Toxicol Appl Pharmacol. 2013;272:519-28 pubmed publisher
    ..The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6h and 24h exposure to 0...
  3. Lee H, Chen Y, Liu Y, Lin K, Chen S, Lin C, et al. Transgenic zebrafish model to study translational control mediated by upstream open reading frame of human chop gene. Nucleic Acids Res. 2011;39:e139 pubmed publisher
    ..Therefore, using the huORFZ embryos allows us to study the regulatory network involved in human uORF(chop)-mediated translational inhibition. ..
  4. Elenbaas J, Maitra D, Liu Y, Lentz S, Nelson B, Hoenerhoff M, et al. A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress. FASEB J. 2016;30:1798-810 pubmed publisher
    ..Elenbaas, J. S., Maitra, D., Liu, Y., Lentz, S. I., Nelson, B., Hoenerhoff, M. J., Shavit, J. A., Omary, M. B. A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress. ..
  5. Wang H, Luo L, Yang D. Loss of Gspt1l disturbs the patterning of the brain central arteries in zebrafish. Biochem Biophys Res Commun. 2017;486:156-162 pubmed publisher
    ..Our results suggest that loss of Gspt1l activates the UPR pathway, which in turn induces ectopic expression of vegfa via Atf4, thus disturbing the patterning of the central arteries. ..
  6. Chen Y, Lu Y, Li I, Hwang S. Zebrafish Agr2 is required for terminal differentiation of intestinal goblet cells. PLoS ONE. 2012;7:e34408 pubmed publisher
    ..However, whether increased endoplasmic reticulum (ER) stress occurs in Agr2(-/-) mice remains a controversial issue...
  7. Chen L, Hu Y, He J, Chen J, Giesy J, Xie P. Responses of the Proteome and Metabolome in Livers of Zebrafish Exposed Chronically to Environmentally Relevant Concentrations of Microcystin-LR. Environ Sci Technol. 2017;51:596-607 pubmed publisher
    ..Identification of proteins and metabolites in liver of zebrafish responsive to MC-LR provides insights into mechanisms of chronic toxicity of MCs. ..
  8. Faltermann S, Prétôt R, Pernthaler J, Fent K. Comparative effects of nodularin and microcystin-LR in zebrafish: 1. Uptake by organic anion transporting polypeptide Oatp1d1 (Slco1d1). Aquat Toxicol. 2016;171:69-76 pubmed publisher
    ..Our study demonstrates that drOatp1d1 functions as an uptake transporter for both MC-LR and nodularin in zebrafish. ..
  9. Paavola J, Schliffke S, Rossetti S, Kuo I, Yuan S, Sun Z, et al. Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. J Mol Cell Cardiol. 2013;58:199-208 pubmed publisher
    ..In human subjects we found an association between ADPKD and IDCM and suggest that PKD mutations contribute to the development of heart failure. ..
  10. Hagenaars A, Vergauwen L, Benoot D, Laukens K, Knapen D. Mechanistic toxicity study of perfluorooctanoic acid in zebrafish suggests mitochondrial dysfunction to play a key role in PFOA toxicity. Chemosphere. 2013;91:844-56 pubmed publisher
    ..Despite this increase in metabolic expenditure, no effects on reproduction were found indicating that the fish seemed to cope with exposure to the tested concentrations of PFOA during the exposure period of 1 month. ..
  11. Weil M, Scholz S, Zimmer M, Sacher F, Duis K. Gene expression analysis in zebrafish embryos: a potential approach to predict effect concentrations in the fish early life stage test. Environ Toxicol Chem. 2009;28:1970-8 pubmed publisher
    ..The results of the present study indicate that gene expression analysis in zebrafish embryos could principally be used to predict effect concentrations in the fish early life stage test. ..
  12. Christen V, Faltermann S, Brun N, Kunz P, Fent K. Cytotoxicity and molecular effects of biocidal disinfectants (quaternary ammonia, glutaraldehyde, poly(hexamethylene biguanide) hydrochloride PHMB) and their mixtures in vitro and in zebrafish eleuthero-embryos. Sci Total Environ. 2017;586:1204-1218 pubmed publisher
    ..Barquat and BAC let to induction of ER stress and inflammation in vitro, and BAC and glutaraldehyde at non-toxic concentrations in vivo, while benzalkonium chloride induced expression of tnf-? only. ..
  13. Jaafar L, Podolsky R, Dynan W. Long-term effects of ionizing radiation on gene expression in a zebrafish model. PLoS ONE. 2013;8:e69445 pubmed publisher
    ..Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue. ..
  14. Damodaran S, Dlugos C, Wood T, Rabin R. Effects of chronic ethanol administration on brain protein levels: a proteomic investigation using 2-D DIGE system. Eur J Pharmacol. 2006;547:75-82 pubmed
    ..In the present study, we have identified some novel protein targets as well as substantiated some putative previous targets of chronic ethanol exposure. ..
  15. Chen Z, Ballar P, Fu Y, Luo J, Du S, Fang S. The E3 ubiquitin ligase gp78 protects against ER stress in zebrafish liver. J Genet Genomics. 2014;41:357-68 pubmed publisher
    ..Together, these data indicate that gp78 plays a critical role in protecting against ER stress in liver...
  16. Hou N, Yang Y, Scott I, Lou X. The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis. Dev Biol. 2017;421:8-15 pubmed publisher
    ..These results show that the existence of a specific export pathway, mediated by a complex containing SCFD1 and STX18 that plays an essential role in secretion of large ECM proteins during chondrogenesis. ..
  17. Santos Ledo A, García Macia M, Campbell P, Gronska M, Marlow F. Kinesin-1 promotes chondrocyte maintenance during skeletal morphogenesis. PLoS Genet. 2017;13:e1006918 pubmed publisher
    ..Cumulatively, we show essential Kif5B functions in promoting cartilage remodeling and chondrocyte maintenance during zebrafish craniofacial morphogenesis. ..
  18. Hu M, Gong H, Lin G, Hu S, Chen M, Huang S, et al. XBP-1, a key regulator of unfolded protein response, activates transcription of IGF1 and Akt phosphorylation in zebrafish embryonic cell line. Biochem Biophys Res Commun. 2007;359:778-83 pubmed
    ..of endogenous IGF1 is transiently induced as XBP-1 splicing during ER stress in parallel to ER chaperone GRP78/Hspa5 and ER resided E3 ubiquitin ligase Synoviolin in ZF4 cells by quantitative PCR...
  19. Eichenbaum J, Cinaroglu A, Eichenbaum K, Sadler K. A zebrafish retinal graded photochemical stress model. J Pharmacol Toxicol Methods. 2009;59:121-7 pubmed publisher
    ..The phenotypic and genetic changes observed from this model can serve as a basis for understanding the pathology of retinal oxidative and cellular stress. These changes may aid our understanding of aging and macular degeneration. ..
  20. Lin Y, White R, Torelli S, Cirak S, Muntoni F, Stemple D. Zebrafish Fukutin family proteins link the unfolded protein response with dystroglycanopathies. Hum Mol Genet. 2011;20:1763-75 pubmed publisher
    ..Together, our results suggest that Fukutin family proteins may play important roles in protein secretion and that the UPR may contribute to the phenotypic spectrum of some dystroglycanopathies in humans...
  21. Dos Anjos N, Schulze T, Brack W, Val A, Schirmer K, Scholz S. Identification and evaluation of cyp1a transcript expression in fish as molecular biomarker for petroleum contamination in tropical fresh water ecosystems. Aquat Toxicol. 2011;103:46-52 pubmed publisher
    ..The data demonstrate the high sensitivity of cyp1a as indicator of oil exposure; further studies should be considered to test its usefulness at known contaminated sites and to evaluate influential factors by, e.g. mesocosm experiments...
  22. Thakur P, Davison J, Stuckenholz C, Lu L, Bahary N. Dysregulated phosphatidylinositol signaling promotes endoplasmic-reticulum-stress-mediated intestinal mucosal injury and inflammation in zebrafish. Dis Model Mech. 2014;7:93-106 pubmed publisher
    ..profile shows enrichment of acute phase response signaling, and the endoplasmic reticulum (ER) stress factors hspa5 and xbp1 are robustly activated in the mutant GI tissue...
  23. Zheng X, Dai W, Chen X, Wang K, Zhang W, Liu L, et al. Caffeine reduces hepatic lipid accumulation through regulation of lipogenesis and ER stress in zebrafish larvae. J Biomed Sci. 2015;22:105 pubmed publisher
    ..of lipogenesis-associated genes (SREBP1, ACC1, CD36 and UCP2), ER stress-associated genes (PERK, IRE1, ATF6 and BIP), the inflammatory cytokine genes (IL-1beta and TNF-alpha) and autophagy associated genes (ATG12 and Beclin-1)...
  24. Brun N, Wehrli B, Fent K. Ecotoxicological assessment of solar cell leachates: Copper indium gallium selenide (CIGS) cells show higher activity than organic photovoltaic (OPV) cells. Sci Total Environ. 2016;543:703-14 pubmed publisher
    ..in genes involved in oxidative stress (cat), hormonal activity (vtg1, ar), metallothionein (mt2), ER stress (bip, chop), and apoptosis (casp9). The effects were dependent on the concentrations of cationic metals in leachates...
  25. Hung I, Cherng B, Hsu W, Lee S. Calnexin is required for zebrafish posterior lateral line development. Int J Dev Biol. 2013;57:427-38 pubmed publisher
    ..These results suggest that calnexin is essential for neuromast formation during lateral line development in the zebrafish. ..
  26. de Preux Charles A, Bise T, Baier F, Sallin P, Jazwinska A. Preconditioning boosts regenerative programmes in the adult zebrafish heart. Open Biol. 2016;6: pubmed publisher
    ..Our results open a new field of research by providing the adult zebrafish as a model system to study remote cardiac preconditioning. ..
  27. Faltermann S, Hutter S, Christen V, Hettich T, Fent K. Anti-Inflammatory Activity of Cyanobacterial Serine Protease Inhibitors Aeruginosin 828A and Cyanopeptolin 1020 in Human Hepatoma Cell Line Huh7 and Effects in Zebrafish (Danio rerio). Toxins (Basel). 2016;8: pubmed publisher
    ..The data further demonstrate that pathways that are influenced by microcystin-LR are not affected by aeruginosin 828A. ..
  28. Qi M, Dang Y, Xu Q, Yu L, Liu C, Yuan Y, et al. Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response. Chemosphere. 2016;157:166-73 pubmed publisher
    ..Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR. ..
  29. Hu M, Bai Y, Zhang C, Liu F, Cui Z, Chen J, et al. Liver-Enriched Gene 1, a Glycosylated Secretory Protein, Binds to FGFR and Mediates an Anti-stress Pathway to Protect Liver Development in Zebrafish. PLoS Genet. 2016;12:e1005881 pubmed publisher
    ..Therefore, Leg1 plays a unique role in protecting liver development under different stress conditions by serving as a secreted signaling molecule/modulator. ..
  30. Monk K, Voas M, Franzini Armstrong C, Hakkinen I, Talbot W. Mutation of sec63 in zebrafish causes defects in myelinated axons and liver pathology. Dis Model Mech. 2013;6:135-45 pubmed publisher
  31. Crosier P, Bardsley A, Horsfield J, Krassowska A, Lavallie E, Collins Racie L, et al. In situ hybridization screen in zebrafish for the selection of genes encoding secreted proteins. Dev Dyn. 2001;222:637-44 pubmed
  32. Liao K, Yan J, Li S, Wang T, Xu W, Mai K, et al. Molecular cloning and characterization of unfolded protein response genes from large yellow croaker (Larimichthys crocea) and their expression in response to dietary fatty acids. Comp Biochem Physiol B Biochem Mol Biol. 2017;203:53-64 pubmed publisher
    ..In this study, four UPR-related genes (GRP78/BiP, ATF6?, XBP1 and CHO) were isolated characterized from large yellow croaker (Larimichthys crocea), and their ..
  33. Ding Y, Long P, Bos J, Shih Y, Ma X, Sundsbak R, et al. A modifier screen identifies DNAJB6 as a cardiomyopathy susceptibility gene. JCI Insight. 2016;1: pubmed
    ..Together, our findings establish a mutagenesis screening strategy that is scalable for systematic identification of genetic modifiers of CM, feasible to suggest therapeutic targets, and expandable to other major human diseases. ..
  34. Vacaru A, Di Narzo A, Howarth D, Tsedensodnom O, Imrie D, Cinaroglu A, et al. Molecularly defined unfolded protein response subclasses have distinct correlations with fatty liver disease in zebrafish. Dis Model Mech. 2014;7:823-35 pubmed publisher
    ..We conclude that a stressed UPR causes steatosis and an adaptive UPR prevents it, demonstrating that this pathway plays dichotomous roles in fatty liver disease. ..
  35. Dai W, Wang K, Zheng X, Chen X, Zhang W, Zhang Y, et al. High fat plus high cholesterol diet lead to hepatic steatosis in zebrafish larvae: a novel model for screening anti-hepatic steatosis drugs. Nutr Metab (Lond). 2015;12:42 pubmed publisher
    ..Additionally, the expression levels of endoplasmic reticulum (ER) stress and lipolytic molecules (atf6, hspa5, hsp90b1, pparab, cpt1a and acox3) were significantly up-regulated in the liver of HF and HFC diets-fed larvae ..
  36. Reverendo M, Soares A, Pereira P, Carreto L, Ferreira V, Gatti E, et al. TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish. RNA Biol. 2014;11:1199-213 pubmed publisher
    ..We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability. ..
  37. Magdeldin S, Blaser R, Yamamoto T, Yates J. Behavioral and proteomic analysis of stress response in zebrafish (Danio rerio). J Proteome Res. 2015;14:943-52 pubmed publisher
    ..in protein abundance following shock exposure, eight proteins were significantly up-regulated (HADHB, hspa8, hspa5, actb1, mych4, atp2a1, zgc:86709, and zgc:86725)...
  38. Melville D, Montero Balaguer M, Levic D, Bradley K, Smith J, Hatzopoulos A, et al. The feelgood mutation in zebrafish dysregulates COPII-dependent secretion of select extracellular matrix proteins in skeletal morphogenesis. Dis Model Mech. 2011;4:763-76 pubmed publisher
  39. Faltermann S, Grundler V, Gademann K, Pernthaler J, Fent K. Comparative effects of nodularin and microcystin-LR in zebrafish: 2. Uptake and molecular effects in eleuthero-embryos and adult liver with focus on endoplasmic reticulum stress. Aquat Toxicol. 2016;171:77-87 pubmed publisher
    ..transcriptional induction of several ER-stress marker genes, including the chaperone glucose regulated protein 78 (bip), the spliced form of x-box binding protein (xbp-1s), the CCAAT-enhancer-binding protein homologous protein (chop) ..
  40. Murayama E, Sarris M, Redd M, Le Guyader D, Vivier C, Horsley W, et al. NACA deficiency reveals the crucial role of somite-derived stromal cells in haematopoietic niche formation. Nat Commun. 2015;6:8375 pubmed publisher
  41. Wang Y, Lin C, Chuang M, Hsieh W, Lan C, Chuang Y, et al. Interspecies protein-protein interaction network construction for characterization of host-pathogen interactions: a Candida albicans-zebrafish interaction study. BMC Syst Biol. 2013;7:79 pubmed publisher
    ..With continued accumulation of interspecies transcriptomics data, the proposed method could be used to explore progressive network rewiring over time, which could benefit the development of network medicine for infectious diseases. ..
  42. Li J, Chen Z, Gao L, Colorni A, Ucko M, Fang S, et al. A transgenic zebrafish model for monitoring xbp1 splicing and endoplasmic reticulum stress in vivo. Mech Dev. 2015;137:33-44 pubmed publisher
    ..The Tg(ef1α:xbp1δ-gfp) transgenic zebrafish provides a useful model for in vivo monitoring xbp1 splicing during development and under ER stress conditions. ..
  43. Schlombs K, Wagner T, Scheel J. Site-1 protease is required for cartilage development in zebrafish. Proc Natl Acad Sci U S A. 2003;100:14024-9 pubmed
    ..This indicates that the cartilage phenoptypes of goz are caused independently of the lipid defects. ..
  44. Brun N, Christen V, Furrer G, Fent K. Indium and indium tin oxide induce endoplasmic reticulum stress and oxidative stress in zebrafish (Danio rerio). Environ Sci Technol. 2014;48:11679-87 pubmed publisher
    ..In(NO3)3 induced the ER stress key gene BiP at mRNA and protein level, as well as atf6, which ultimately led to induction of the important pro-apoptotic marker ..