Affinage

HSPA1B

Heat shock 70 kDa protein 1B · UniProt P0DMV9

Length
641 aa
Mass
70.1 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPA1B encodes an inducible HSP70-family molecular chaperone with ATP-dependent protein-folding activity that fulfills essential, sex-specific roles in male meiosis and broad cytoprotective functions in somatic and cancer cells. In male germ cells, HSPA1B associates with synaptonemal complexes during pachytene, is required for their desynapsis at the diplotene transition, and chaperones CDC2 kinase to enable CDC2/cyclin B1 complex assembly and kinase activation needed for the meiotic G2/M transition; its protein stability in spermatocytes depends on Bat3-mediated protection from polyubiquitylation and proteasomal degradation (PMID:8622925, PMID:9409676, PMID:9247342, PMID:18678708). HSPA1B transcription is induced by hypoxia via HIF-1α binding a promoter HRE and by hypertonic stress via a TonE element, while its mRNA is post-transcriptionally repressed by miR-15a and miR-23a-5p targeting the 3′-UTR (PMID:18844219, PMID:16819288, PMID:24481955, PMID:33206547). In cancer cells, HSPA1B depletion triggers lysosomal membrane permeabilization through loss of LEDGF-dependent lysosomal stabilization, activates mitochondria-dependent apoptosis, and suppresses cell migration and invasion (PMID:17363574, PMID:18822209, PMID:19914824).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Establishing that HSP70-2 is a synaptonemal-complex-associated protein essential for male meiosis resolved a long-standing question of whether individual HSP70 family members have non-redundant developmental roles.

    Evidence Gene knockout in mice with immunocytology and nuclear fractionation of spermatocytes

    PMID:8601336 PMID:8622925

    Open questions at the time
    • Mechanism by which HSP70-2 stabilizes or remodels synaptonemal complexes was unknown
    • Why female meiosis is unaffected remained unexplained
  2. 1997 High

    Defining the meiotic arrest point (failure of desynapsis at late pachytene) and identifying CDC2 kinase as a direct HSP70-2 client revealed the dual mechanism—structural role at synaptonemal complexes and chaperone-dependent cell-cycle activation—through which HSP70-2 drives meiosis I.

    Evidence Hsp70-2 KO mouse histology with stage markers; co-immunoprecipitation of HSP70-2–CDC2, in vitro reconstitution of CDC2/cyclin B1 activity

    PMID:9247342 PMID:9409676

    Open questions at the time
    • Whether HSP70-2 has additional meiotic substrates beyond CDC2 was not tested
    • Structural basis of HSP70-2 interaction with synaptonemal complex proteins was unresolved
  3. 2001 Medium

    Identification of testis-specific DnaJ cochaperones (MSJ-1, DjA4) that partner with HSP70-2 established that its chaperone cycle in germ cells uses dedicated J-domain cofactors rather than housekeeping cochaperones.

    Evidence Co-immunoprecipitation, in vitro binding, immunofluorescence colocalization in spermatogenic cells; in vitro ATPase and luciferase aggregation assays

    PMID:11466217 PMID:15047721

    Open questions at the time
    • Whether MSJ-1 or DjA4 are required in vivo for HSP70-2 function was not shown genetically
    • Stoichiometry and selectivity of cochaperone pairing were not determined
  4. 2006 Medium

    Discovery that HSP70-2 associates with transition proteins 1/2 in condensing spermatids extended its functional scope beyond meiosis into post-meiotic chromatin remodeling during spermiogenesis.

    Evidence Mass-spectrometry-based proteomics of genome-organizing proteins in condensing spermatids

    PMID:17035236

    Open questions at the time
    • Functional consequence of disrupting the HSP70-2–transition protein interaction was not tested
    • Whether HSP70-2 is required for histone-to-protamine transition was unknown
  5. 2006 High

    Mapping transcriptional control elements—a HIF-1α-responsive HRE and a TonE site—on the HSPA1B promoter explained how this chaperone is induced under hypoxia and osmotic stress in somatic cells.

    Evidence Luciferase reporters with site-directed mutagenesis, ChIP for HIF-1α, HIF-1α siRNA

    PMID:16819288 PMID:18844219

    Open questions at the time
    • Chromatin context and combinatorial regulation with heat-shock elements were not fully dissected
    • Whether these regulatory elements are active in all somatic tissues was not tested
  6. 2007 Medium

    Demonstrating that HSP70-2 depletion causes lysosomal membrane permeabilization via loss of LEDGF expression, and separately triggers mitochondrial apoptosis, placed HSP70-2 at the nexus of two distinct pro-survival pathways in cancer cells.

    Evidence siRNA/shRNA knockdown in cancer cell lines, lysosomal and mitochondrial apoptosis pathway assays, xenograft models

    PMID:17363574 PMID:18822209

    Open questions at the time
    • Direct molecular mechanism linking HSP70-2 to LEDGF transcription or stability was not identified
    • Whether the lysosomal and mitochondrial pathways are independent or connected was unresolved
  7. 2008 High

    Bat3/Scythe was identified as a critical upstream stabilizer of HSP70-2 protein: Bat3 loss leads to HSP70-2 polyubiquitylation and proteasomal degradation, phenocopying the Hsp70-2 KO meiotic defects, and revealing a post-translational quality-control axis for this chaperone.

    Evidence Bat3 conditional KO mice, ubiquitylation assays, proteasome inhibitor rescue of HSP70-2 protein

    PMID:18678708

    Open questions at the time
    • The E3 ligase responsible for HSP70-2 ubiquitylation in the absence of Bat3 was not identified
    • Whether Bat3 directly shields HSP70-2 or acts indirectly was not resolved
  8. 2008 Medium

    Detection of HSF1, HSF2, SP1, and RNA Pol II pre-loaded on the Hspa1b promoter in mature spermatozoa suggested a bookmarking mechanism for rapid HSPA1B transcription during zygotic genome activation after fertilization.

    Evidence Chromatin immunoprecipitation in epididymal spermatozoa

    PMID:18434628 PMID:19336471

    Open questions at the time
    • Functional necessity of promoter bookmarking for early embryonic Hspa1b expression was not demonstrated by loss-of-function
    • Whether transcription actually initiates from this bookmarked state after fertilization was not directly shown
  9. 2014 Medium

    Identification of miR-15a and later miR-23a-5p as direct negative regulators of HSPA1B via its 3′-UTR established a post-transcriptional regulatory layer, relevant to spermatogenic defects (varicocele) and tonicity-responsive renal cell survival.

    Evidence Dual-luciferase 3′-UTR reporter assays, miRNA overexpression/inhibition, clinical sperm and in vivo kidney miRNA-mRNA correlation

    PMID:24481955 PMID:33206547

    Open questions at the time
    • Contribution of miR-15a to HSPA1B regulation in non-reproductive tissues was not tested
    • Relative quantitative impact of each miRNA versus transcriptional regulation was not compared
  10. 2016 Medium

    Comprehensive knockdown studies in breast and other cancer types consolidated the view that HSPA1B supports tumor cell proliferation, migration, invasion, and epithelial–mesenchymal transition while suppressing apoptosis.

    Evidence shRNA knockdown in multiple cancer lines, proliferation/apoptosis/migration/invasion assays, western blot for cyclins/CDKs/caspases/EMT markers, xenograft models

    PMID:19914824 PMID:25213699 PMID:27658496

    Open questions at the time
    • Direct chaperone clients mediating the pro-invasive and EMT phenotypes were not identified
    • Whether effects are HSPA1B-specific or shared with other inducible HSP70 paralogues was not resolved
  11. 2022 Medium

    Temperature-dependent binding of UBQLN2 to HSPA1B linked the ubiquilin proteostasis network to the heat-shock response, with ALS/FTD-associated UBQLN2 mutations attenuating this conformational switch.

    Evidence In vitro binding and tryptophan fluorescence assays with wild-type and mutant UBQLN2 at 37°C and 42°C

    PMID:36423739

    Open questions at the time
    • Cellular relevance of UBQLN2–HSPA1B interaction during heat shock was not demonstrated
    • Whether the interaction involves HSPA1B client handoff to the proteasome was not tested
  12. 2024 Medium

    Placement of HSPA1B upstream of AKT in a TREM-2-regulated macrophage exosome pathway affecting renal fibrosis expanded HSPA1B function into intercellular signaling and tissue remodeling.

    Evidence TREM-2 KO macrophages, exosome isolation, RNA-seq, HSP70 inhibitor (VER-155008) and AKT inhibitor epistasis, in vivo fibrosis model

    PMID:39657110

    Open questions at the time
    • Whether HSPA1B acts as a cargo, a signaling mediator, or a chaperone within exosomes was not determined
    • Specificity of VER-155008 for HSPA1B versus other HSP70 family members was not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ubiquitin ligase targeting HSPA1B in the absence of Bat3, the direct client proteins that mediate HSPA1B's pro-invasive and anti-apoptotic effects in cancer cells, the structural basis of its interaction with synaptonemal complex components, and the functional redundancy versus specificity relative to HSPA1A and HSPA2.
  • E3 ligase for HSPA1B ubiquitylation unidentified
  • Direct chaperone clients in cancer invasion pathway unknown
  • Paralog-specific versus shared functions with HSPA1A/HSPA2 not systematically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
BAT3CDC2DNAJA4LEDGFMSJ1SYCP3UBQLN2
Complex memberships
CDC2/cyclin B1 (as chaperone)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 HSP70-2 (HSPA2/Hsp70-2) is associated with synaptonemal complexes in the nucleus of meiotic spermatocytes; targeted disruption of Hsp70-2 in mice results in structural abnormalities of synaptonemal complexes by late prophase, failure of meiosis, spermatocyte apoptosis, and male infertility, while females are unaffected. Gene knockout (targeted gene disruption), immunocytology of synaptonemal complexes, nuclear fractionation Proceedings of the National Academy of Sciences of the United States of America High 8622925
1997 HSP70-2 is required specifically for synaptonemal complex desynapsis during meiotic prophase; in Hsp70-2(-/-) mice synaptonemal complexes form and reach late pachytene but fail to desynapse, preventing diplotene formation and blocking transition to meiotic divisions. Hsp70-2 knockout mouse analysis, histology, immunohistochemistry, mRNA/antigen expression analysis of stage markers (cyclin A1) Development (Cambridge, England) High 9409676
1997 HSP70-2 acts as a molecular chaperone for CDC2 kinase in mouse testis: it physically interacts with CDC2, is required for CDC2/cyclin B1 complex formation, and its absence abolishes CDC2 kinase activity for histone H1. Addition of HSP70-2 to Hsp70-2(-/-) testis extracts restores CDC2/cyclin B1 complex formation and CDC2 kinase activity in vitro. Immunoprecipitation-coupled western blot, in vitro reconstitution, histone H1 kinase assay, Hsp70-2 knockout mice Development (Cambridge, England) High 9247342
1996 HSP70-2 is localized to both cytoplasmic and nuclear fractions in mouse spermatocytes; immunocytological analysis shows HSP70-2 is specifically associated with synaptonemal complexes at pachytene and diplotene stages in mouse and hamster, but not in fetal oocyte synaptonemal complexes, demonstrating a sexually dimorphic localization. Subcellular fractionation, two-dimensional gel electrophoresis, immunocytology of surface-spread synaptonemal complexes, RT-PCR Chromosoma High 8601336
2001 MSJ-1, a testis-specific DnaJ cochaperone, physically interacts with Hsp70-2 and can be co-immunoprecipitated with Hsp70-2 from spermatogenic cells; in late differentiating spermatids, MSJ-1 colocalizes with Hsp70-2 at the developing acrosome and postnuclear region. In vitro binding assay with recombinant proteins, co-immunoprecipitation, immunofluorescence colocalization Biology of reproduction Medium 11466217
2004 DjA4 (a type I DnaJ cochaperone) can modulate the ATPase activity of Hsp70-2 and suppresses luciferase aggregation together with Hsp70-2; in vitro, Hsp70-2 behaves similarly to Hsp70-1 in ATPase stimulation and aggregation suppression assays, confirming it has chaperone activity comparable to canonical Hsp70. In vitro ATPase assay, luciferase refolding and aggregation suppression assays Journal of biochemistry Medium 15047721
2006 HSPA2 (Hsp70-2) acquires new functions in post-meiotic spermatids, becoming tightly associated with transition proteins 1 and 2 (major spermatid DNA-packaging proteins), identifying it as the first known transition protein chaperone during spermiogenesis. Global proteomic approach (mass spectrometry) to identify genome-organizing proteins in condensing spermatids, functional co-association analysis The Journal of biological chemistry Medium 17035236
2007 Hsp70-2 depletion in cancer cells triggers lysosomal membrane permeabilization and cathepsin-dependent, caspase-independent cell death. LEDGF (lens epithelium-derived growth factor) was identified as an Hsp70-2-regulated guardian of lysosomal stability: Hsp70-2 regulates LEDGF expression, which in turn stabilizes lysosomal membranes in human cancer cells. RNAi knockdown (siRNA), lysosomal membrane permeabilization assay, ectopic overexpression, in vivo xenograft, cell death assays Cancer research Medium 17363574
2008 Bat3/Scythe is a critical regulator of Hsp70-2 protein stability in spermatogenesis: Bat3 deficiency causes polyubiquitylation and subsequent proteasomal degradation of Hsp70-2. Inhibition of proteasomal degradation restores Hsp70-2 protein levels. Loss of Hsp70-2 protein (despite normal transcript levels) is associated with abnormal synaptonemal complex assembly/disassembly and male germ cell apoptosis. Bat3 conditional knockout mice, western blot for Hsp70-2 protein and mRNA, ubiquitylation assays, proteasome inhibitor rescue experiments, SYCP3/gamma-H2AX/Rad51 immunostaining The Journal of cell biology High 18678708
2008 HSF1 and HSF2 transcription factors are present in epididymal spermatozoa and bind the Hspa1b promoter in vivo; HSF2 binding to the Hspa1b promoter increases from early to late spermatids, suggesting these factors bookmark the Hspa1b promoter to allow rapid gene expression during minor zygotic genome activation after fertilization. Chromatin immunoprecipitation (ChIP), western blot, immunofluorescence Biology of reproduction Medium 18434628
2009 RNA polymerase II is present in epididymal spermatozoa and bound to the Hspa1b promoter, supporting a model in which pre-loaded transcription machinery (HSF1, HSF2, SP1, Pol II) enables rapid Hspa1b expression after fertilization during minor zygotic genome activation. Chromatin immunoprecipitation (ChIP), western blot Reproduction (Cambridge, England) Medium 19336471
2009 Hypoxia induces HSP70-2 expression in cancer cells through direct binding of HIF-1α to a hypoxia-responsive element (HRE1) at position -446 of the HSP70-2 promoter; mutation of HRE1 abrogates hypoxia-induced promoter activity, and upregulation of HSP70-2 enhances resistance to hypoxia-induced apoptosis. Luciferase reporter assays, chromatin immunoprecipitation, site-directed mutagenesis, HIF-1α siRNA knockdown, western blot International journal of cancer High 18844219
2006 The HSP70-2 promoter contains a tonicity-responsive enhancer (TonE) site at -135 that is essential for induction by hypertonic stress in human kidney cells; site-directed mutagenesis of this TonE site abolishes hypertonicity-induced promoter activation, demonstrating TonEBP as a key regulator of HSPA1B under osmotic stress. Luciferase reporter assays with deletion and site-directed mutagenesis, transfection in human embryonic kidney epithelial cells and fibroblasts Experimental & molecular medicine Medium 16819288
2004 A HSPA1B promoter polymorphism (HSPA1B-179C>T) in linkage disequilibrium with HSPA1B1267A>G is functionally associated with variable production of HSPA1A and HSPA1B mRNA after LPS stimulation in mononuclear cells, with the C/C homozygotes showing lower HSPA1A and HSPA1B mRNA levels after 8 hours of LPS stimulation. Promoter sequencing, RT-PCR after LPS stimulation, linkage disequilibrium analysis Intensive care medicine Medium 15232679
2014 HSP70-2 knockdown in renal cell carcinoma cells significantly reduces cellular growth, colony formation, migration, and invasion; HSP70-2 protein is predominantly localized in the cytoplasm and colocalizes with endoplasmic reticulum, mitochondria, Golgi body, and plasma membrane but not the nuclear envelope. shRNA knockdown, cell proliferation assay, colony formation, migration/invasion assays, immunofluorescence colocalization with organelle markers Tumour biology Medium 25213699
2010 HSP70-2 knockdown in bladder urothelial carcinoma cells significantly suppresses cellular motility, invasion, and tumor growth in vivo in xenograft models, demonstrating a functional role for HSP70-2 in cancer cell migration and invasion. shRNA knockdown, migration assay, invasion assay, in vivo xenograft tumor growth European journal of cancer Medium 19914824
2014 miR-15a directly binds the 3'-UTR of HSPA1B mRNA and represses its expression; miR-15a and HSPA1B show inverse expression correlation in sperm from varicocele patients. Dual-luciferase 3'-UTR reporter assay, miRNA overexpression/inhibition, qPCR in clinical sperm samples Reproduction (Cambridge, England) Medium 24481955
2016 HSP70-2 depletion in breast cancer cells (MDA-MB-231, MCF7) reduces cellular growth, motility, invasion, and tumor xenograft growth, and is associated with reduced expression of cyclins, CDKs, anti-apoptotic molecules, and mesenchymal markers, and increased expression of CDK inhibitors, caspases, pro-apoptotic molecules, and epithelial markers. Plasmid-driven shRNA knockdown, proliferation/apoptosis/senescence/migration/invasion assays, flow cytometry, western blot for pathway molecules, in vivo xenograft Journal of experimental & clinical cancer research Medium 27658496
2008 HSP70-2 knockdown in hepatocellular carcinoma (HCC) cells induces mitochondria-dependent apoptosis, characterized by cytochrome c release, caspase-9 and caspase-3 activation, loss of mitochondrial membrane potential, Bax upregulation, and Bcl-2 downregulation. shRNA knockdown, flow cytometry (mitochondrial membrane potential), western blot for apoptosis pathway proteins, MTT cell proliferation assay Zhonghua gan zang bing za zhi Medium 18822209
2016 Recombinant human Tat-Hsp70-2 produced in E. coli shows ATPase activity and, when added to human neuroblastoma SH-SY5Y cells under hydrogen peroxide or 6-hydroxydopamine stress, partially protects cells from these cytotoxic treatments. Recombinant protein expression and purification, ATPase activity assay, cell viability assay Protein expression and purification Medium 27405095
2022 UBQLN2 physically binds HSPA1B in vitro, and this interaction is temperature-regulated: raising temperature from 37°C to 42°C dramatically increases UBQLN2-HSPA1B binding, while restoration to 37°C decreases it. ALS/FTD-associated UBQLN2 mutants show attenuated conformational changes at 42°C but retain similar HSPA1B binding. In vitro protein binding assay, intrinsic tryptophan fluorescence measurement, comparison of wild-type vs. ALS/FTD UBQLN2 mutants Biochimica et biophysica acta. General subjects Medium 36423739
2020 miR-23a-5p is a tonicity-responsive miRNA that targets HSPA1B 3'-UTR: downregulation of miR-23a-5p under hypertonic stress promotes HSPA1B expression, increasing renal cell survival, while miR-23a-5p overexpression suppresses HSPA1B and reduces cell viability. An inverse correlation between miR-23a-5p and HSPA1B is confirmed in mouse renal inner medulla in vivo. miRNA profiling, dual-luciferase 3'-UTR reporter assay, miRNA knockdown/overexpression, cell viability assay, RNA sequencing, in vivo mouse kidney analysis American journal of physiology. Cell physiology Medium 33206547
2024 TREM-2 deficiency in macrophages increases the MMP-9/TIMP-1 ratio in their secreted exosomes via the HSPa1b/AKT pathway; inhibition of HSPa1b (using VER-155008) or AKT reverses the anti-fibrotic effect, placing HSPa1b upstream of AKT in this macrophage exosome-mediated pathway that alleviates renal fibrosis. Macrophage TREM-2 knockout, exosome isolation, RNA-seq, in vitro and in vivo fibrosis models, chemical inhibitors (VER-155008, Ly294002), AAV-shTREM-2 in vivo American journal of physiology. Renal physiology Medium 39657110
2002 A 3'-UTR sequence variant of the porcine inducible hsp70.2 gene increases mRNA half-life in reporter gene assays, demonstrating post-transcriptional regulation of hsp70.2 mRNA stability by 3'-UTR sequence variation. Reporter gene (mRNA stability) assay with 3'-UTR sequence variants, comparative sequence analysis Biochimica et biophysica acta Medium 12393191

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proceedings of the National Academy of Sciences of the United States of America 449 8622925
1997 HSP70-2 is required for desynapsis of synaptonemal complexes during meiotic prophase in juvenile and adult mouse spermatocytes. Development (Cambridge, England) 194 9409676
1997 HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes. Development (Cambridge, England) 175 9247342
1999 Role of heat shock protein HSP70-2 in spermatogenesis. Reviews of reproduction 162 10051099
2007 Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer. Cancer research 109 17363574
1993 Polymorphic analysis of the human MHC-linked heat shock protein 70 (HSP70-2) and HSP70-Hom genes in insulin-dependent diabetes mellitus (IDDM). Scandinavian journal of immunology 109 7901896
2006 Post-meiotic shifts in HSPA2/HSP70.2 chaperone activity during mouse spermatogenesis. The Journal of biological chemistry 101 17035236
1996 HSP70-2 is part of the synaptonemal complex in mouse and hamster spermatocytes. Chromosoma 85 8601336
1999 A hsp70-2 mutation recognized by CTL on a human renal cell carcinoma. Journal of immunology (Baltimore, Md. : 1950) 78 9973436
1993 Chromosomal localization of five murine HSP70 gene family members: Hsp70-1, Hsp70-2, Hsp70-3, Hsc70t, and Grp78. Genomics 77 8486356
2001 Decreased expression of the heat shock protein hsp70-2 is associated with the pathogenesis of male infertility. Fertility and sterility 71 11730740
1996 Developmentally regulated expression of Hsp70-2 and a Hsp70-2/lacZ transgene during spermatogenesis. Developmental biology 71 8631503
2007 Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children. Pediatric research 67 17314700
2010 Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion. European journal of cancer (Oxford, England : 1990) 66 19914824
2003 Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury. Critical care medicine 62 12544996
2003 Polymorphism of the stress protein HSP70-2 gene is associated with the susceptibility to the nasopharyngeal carcinoma. Cancer letters 60 12691826
1995 The major histocompatibility complex region marked by HSP70-1 and HSP70-2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups. Blood 59 7579351
2016 Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. Journal of experimental & clinical cancer research : CR 54 27658496
2009 Transcriptional upregulation of HSP70-2 by HIF-1 in cancer cells in response to hypoxia. International journal of cancer 54 18844219
2016 Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth. BMC cancer 50 27473057
2005 Hsp70-2 is required for tumor cell growth and survival. Cell cycle (Georgetown, Tex.) 50 15970673
2005 Polymorphism of the TNF-alpha, HSP70-2, and CD14 genes increases susceptibility to severe acute pancreatitis. Pancreas 49 15714129
2008 Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis. The Journal of cell biology 47 18678708
1993 HLA-linked heat-shock protein 70 (HSP70-2) gene polymorphism and celiac disease. Tissue antigens 47 8096093
2005 Association of hsp70-2 and hsp-hom gene polymorphisms with risk of acute high-altitude illness in a Chinese population. Cell stress & chaperones 44 16333988
2008 Interaction of serum 70-kDa heat shock protein levels and HspA1B (+1267) gene polymorphism with disease severity in patients with chronic heart failure. Cell stress & chaperones 41 18759004
2005 Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease. Scandinavian journal of gastroenterology 40 16165702
2003 HSP70-2 (HSPA1B) is associated with noncognitive symptoms in late-onset Alzheimer's disease. Journal of geriatric psychiatry and neurology 40 12967056
2014 Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele. Reproduction (Cambridge, England) 39 24481955
1995 Polymorphism of the heat-shock protein gene HSP70-2 in systemic lupus erythematosus. British journal of rheumatology 39 7551654
2020 FLOURY ENDOSPERM11-2 encodes plastid HSP70-2 involved with the temperature-dependent chalkiness of rice (Oryza sativa L.) grains. The Plant journal : for cell and molecular biology 38 32215974
2001 MSJ-1, a mouse testis-specific DnaJ protein, is highly expressed in haploid male germ cells and interacts with the testis-specific heat shock protein Hsp70-2. Biology of reproduction 38 11466217
1998 HSP70-2 heat-shock protein of mouse spermatogenic cells. The Journal of experimental zoology 36 9723183
2004 The septic shock associated HSPA1B1267 polymorphism influences production of HSPA1A and HSPA1B. Intensive care medicine 34 15232679
2004 Polymorphism of stress protein HSP70-2 gene in Tunisians: susceptibility implications in type 2 diabetes and obesity. Diabetes & metabolism 33 15223990
1999 Polymorphism of heat-shock protein gene HSP70-2 in Crohn disease: possible genetic marker for two forms of Crohn disease. Scandinavian journal of gastroenterology 33 10466882
1996 The 8.5-kb PstI allele of the stress protein gene, Hsp70-2: an independent risk factor for systemic lupus erythematosus in African Americans? Human immunology 33 8655362
2010 HSFs and regulation of Hsp70.1 (Hspa1b) in oocytes and preimplantation embryos: new insights brought by transgenic and knockout mouse models. Cell stress & chaperones 32 21053113
2005 Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and schizophrenia. Neuroscience research 30 15963589
2015 Simultaneous Administration of Dexamethasone and Vitamin E Reversed Experimental Varicocele-induced Impact in testicular tissue in Rats; Correlation with Hsp70-2 Chaperone Expression. International braz j urol : official journal of the Brazilian Society of Urology 29 26401872
2006 Involvement of -308 TNF-alpha and 1267 Hsp70-2 polymorphisms and zinc status in the susceptibility of coronary artery disease (CAD) in old patients. Biogerontology 29 16953332
2005 1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. Mechanisms of ageing and development 29 15992611
2001 Genetic variation in the stress protein hsp70-2 gene is highly associated with obesity. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 29 11319647
2017 Heat shock protein 70-2 (HSP70-2) a novel cancer testis antigen that promotes growth of ovarian cancer. American journal of cancer research 28 28670489
1998 Heterogeneous patterns of constitutive and heat shock induced expression of HLA-linked HSP70-1 and HSP70-2 heat shock genes in human melanoma cell lines. Melanoma research 28 9918409
2009 Diminished reproductive potential of male mice in response to selenium-induced oxidative stress: involvement of HSP70, HSP70-2, and MSJ-1. Journal of biochemical and molecular toxicology 27 19367646
2003 Heat-shock protein HSP70-2 genotypes in patients with Crohn's disease: a more severe clinical course with intestinal complications in presence of the PstI-polymorphism. European journal of medical research 23 12730033
2009 Selenium variation induced oxidative stress regulates p53 dependent germ cell apoptosis: plausible involvement of HSP70-2. European journal of nutrition 22 19247702
2004 Modulation of chaperone activities of Hsp70 and Hsp70-2 by a mammalian DnaJ/Hsp40 homolog, DjA4. Journal of biochemistry 21 15047721
2001 Expression of Hsp70-2 in unilateral cryptorchid testis of rhesus monkey during germ cell apoptosis. Endocrine 21 11887939
1996 Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain. Brain research. Molecular brain research 21 8738139
2014 Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population. Gene 20 25108126
2002 A 3'-UTR variant of the inducible porcine hsp70.2 gene affects mRNA stability. Biochimica et biophysica acta 20 12393191
2014 Targeting the testis-specific heat-shock protein 70-2 (HSP70-2) reduces cellular growth, migration, and invasion in renal cell carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 25213699
1994 HSP70-2 9.0 kb variant is in linkage disequilibrium with the HLA-B and DRB1* alleles associated with clozapine-induced agranulocytosis. The Journal of clinical psychiatry 18 7961560
2008 Interaction of HSF1 and HSF2 with the Hspa1b promoter in mouse epididymal spermatozoa. Biology of reproduction 17 18434628
2006 The role of tonicity responsive enhancer sites in the transcriptional regulation of human hsp70-2 in response to hypertonic stress. Experimental & molecular medicine 17 16819288
2014 Association between the HSPA1B ±1267A/G polymorphism and cancer risk: a meta-analysis of 14 case-control studies. Asian Pacific journal of cancer prevention : APJCP 16 25169537
1999 Completion of meiosis is not always required for acrosome formation in HSP70-2 null mice. Biology of reproduction 16 10456862
2009 RNA polymerase II interacts with the Hspa1b promoter in mouse epididymal spermatozoa. Reproduction (Cambridge, England) 15 19336471
2004 Location of promoter elements necessary and sufficient to direct testis-specific expression of the Hst70/Hsp70.2 gene. The Biochemical journal 15 14766014
2016 Association of heat shock protein70-2 (HSP70-2) gene polymorphism with obesity. Annals of human biology 14 26728972
2007 Sequence analysis of HSPA1A and HSPA1B in a multi-ethnic study population. DNA sequence : the journal of DNA sequencing and mapping 14 17364813
2006 Promoter of the heat shock testis-specific Hsp70.2/Hst70 gene is active in nervous system during embryonic development of mice. Anatomy and embryology 14 17047988
2001 Expression of HSP70-2 gene during germ cell apoptosis in rat unilateral cryptorchid testes. Archives of andrology 14 11297064
2008 Polymorphisms of the TNF, CD14, and HSPA1B genes in patients with acute alcohol-induced pancreatitis. Pancreas 13 18580445
1996 Distinct transcripts are recognized by sense and antisense riboprobes for a member of the murine HSP70 gene family, HSP70.2, in various reproductive tissues. Molecular reproduction and development 13 9110944
2017 Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L) and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study. PloS one 12 28182740
2012 Association of hsp70-2 (+1267A/G), hsp70-hom (+2437T/C), HMOX-1 (number of GT repeats) and TNF-alpha (+489G/A) polymorphisms with COPD in Croatian population. Clinical biochemistry 12 22542718
2012 Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease. Diagnostic pathology 12 22834788
2009 Analysis of Msx1 and Msx2 transactivation function in the context of the heat shock 70 (Hspa1b) gene promoter. Biochemical and biophysical research communications 12 19338779
2020 Identification of Plasmodium falciparum HSP70-2 as a resident of the Plasmodium export compartment. Heliyon 11 32529065
2019 Association of HSPA1B Polymorphisms with Paranoid Schizophrenia in a Polish Population. Neuromolecular medicine 11 31642026
2020 Inhibition of orf virus replication in goat skin fibroblast cells by the HSPA1B protein, as demonstrated by iTRAQ-based quantitative proteome analysis. Archives of virology 10 32876795
2013 Crohn's disease and polymorphism of heat shock protein gene HSP70-2 in the Chinese population. Journal of gastroenterology and hepatology 10 23425104
2000 Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican mestizo population. Genes and immunity 10 11196683
1994 A pentanucleotide tandem duplication polymorphism in the 3' untranslated region of the HLA-linked heat-shock protein 70-2 (HSP70-2) gene. Human genetics 10 7959705
2019 HSPA1L and HSPA1B gene polymorphisms and haplotypes are associated with idiopathic male infertility in Iranian population. European journal of obstetrics, gynecology, and reproductive biology 9 31228677
2013 Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean population. Immunological investigations 9 24303776
2012 Tumor cell expression of heat shock protein (HSP) 72 is influenced by HSP72 [HSPA1B A(1267)G] polymorphism and predicts survival in small Cell lung cancer (SCLC) patients. Cancer investigation 9 22468780
2007 Crohn's disease and polymorphism of heat shock protein gene HSP70-2 in the Tunisian population. European journal of gastroenterology & hepatology 9 17301649
2019 Increase of Hspa1a and Hspa1b genes in the resting B cells of Sirt1 knockout mice. Molecular biology reports 8 31102152
2002 Expression of Hsp70-2 in rhesus monkey testis during germ cell apoptosis induced by testosterone undecanoate. Contraception 8 12443970
2020 A novel tonicity-responsive microRNA miR-23a-5p modulates renal cell survival under osmotic stress through targeting heat shock protein 70 HSPA1B. American journal of physiology. Cell physiology 7 33206547
2020 Genetic association study of a novel indel polymorphism in HSPA1B with the risk of sudden cardiac death in the Chinese populations. Forensic science international 7 33309992
2009 [Hypoxia induces heat shock protein HSP70-2 expression in a HIF-1 dependent manner]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 7 19335985
2008 Polymorphisms of the MCP-1 and HSP70-2 genes in Korean patients with alcoholic chronic pancreatitis. Digestive diseases and sciences 7 17940904
2015 Mutations in HSP70-2 gene change the susceptibility to clinical mastitis in Chinese Holstein. Gene 6 25592821
2008 [Inhibition of HSP70-2 expression by RNA interference induces apoptosis of human hepatocellular carcinoma cells]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 6 18822209
2016 Recombinant human Tat-Hsp70-2: A tool for neuroprotection. Protein expression and purification 5 27405095
2015 Genetic polymorphisms of hspa1b and hspa1l in infertile men. JPMA. The Journal of the Pakistan Medical Association 5 26160076
2006 Polymorphisms of heat shock protein-70 (HSPA1B and HSPA1L loci) do not influence infection or outcome risk in critically ill surgical patients. Shock (Augusta, Ga.) 5 16525348
1998 Analysis of the 5'-flanking regions of the MHC-linked Hsp70-2 and Hsp70-3 genes of the rat. Biochimica et biophysica acta 5 9434152
2024 Exosomes derived from TREM-2 knocked-out macrophages alleviated renal fibrosis via HSPa1b/AKT pathway. American journal of physiology. Renal physiology 4 39657110
2022 Next Generation Sequencing of Genotype Variants and Genetic Association between Heat Shock Proteins HSPA1B Single Nucleotide Polymorphism at the g.31829044 Locus and Heat Tolerance: A Pilot Quasi-Experimental Study. Biomolecules 4 36291674
2022 UBQLN2 undergoes a reversible temperature-induced conformational switch that regulates binding with HSPA1B: ALS/FTD mutations cripple the switch but do not destroy HSPA1B binding. Biochimica et biophysica acta. General subjects 4 36423739
2017 [The GG genotype of the HSPA1B gene is associated with increased risk of glaucoma in northern Iran]. Molekuliarnaia biologiia 4 28251963
2020 Erratum: Heat shock protein 70-2 (HSP70-2) a novel cancer testis antigen that promotes growth of ovarian cancer. American journal of cancer research 3 32642300
1999 Heat-shock protein (HSP70-2) allelic frequencies in three distinct Mexican populations. Genes and immunity 3 11197308
2025 N6-methyladenosine (m6A) modification regulates HSPA1A and HSPA1B expression in Müller cells under high glucose stress. Experimental eye research 2 39922527