Affinage

HSPA2

Heat shock-related 70 kDa protein 2 · UniProt P54652

Length
639 aa
Mass
70.0 kDa
Annotated
2026-06-10
58 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSPA2 is a testis-enriched HSP70-family chaperone that governs male germ cell maturation while also serving broader cytoprotective and signaling roles in somatic tissues (PMID:10952940, PMID:17035236). In spermatogenesis it acts at two stages: during meiotic prophase I a tNASP-HSPA2-CDC2 complex on the synaptonemal complex sequesters CDC2 away from cyclin B1, and linker-histone binding to tNASP stimulates HSPA2 ATPase activity to gate the G2→M transition (PMID:19553603); during post-meiotic spermiogenesis HSPA2 becomes the chaperone for the genome-condensing transition proteins TP1 and TP2, working with PARP1/PARP2 in a spermatid-specific genome-reorganizing complex (PMID:17035236, PMID:19607827). On the mature sperm surface HSPA2 nucleates large multimeric complexes with SPAM1 and ARSA whose capacitation-driven, membrane-fluidity- and PKA/tyrosine-kinase-dependent translocation to the apical head enables zona pellucida recognition; loss of HSPA2 abolishes sperm-zona binding (PMID:23209833, PMID:23247813, PMID:10952940). HSPA2 protein abundance is set by opposing ubiquitin-proteasome activities: it is stabilized by BAG6 in germ cells and by the deubiquitinase USP20 in somatic cells, and is targeted for degradation by the E3 ligase RNF144A, which restrains tumor cell proliferation through HSPA2 turnover (PMID:18678708, PMID:26153132, PMID:36636478, PMID:31406303). Beyond reproduction, HSPA2 maintains basal keratinocytes in an undifferentiated state and restrains epidermal inflammatory cytokine secretion (PMID:28786487, PMID:40287440), confers resistance to proteotoxic stress in somatic cells (PMID:22397456), suppresses innate antiviral immunity by binding TBK1 and blocking HERC5-mediated K63-linked ubiquitination of TBK1 at K608 to inhibit IRF3 activation and type I interferon production (PMID:41934636), and regulates the first embryonic cell-fate decision in 2-cell mouse embryos via interaction with CARM1 (PMID:40063400).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Establishing the molecular identity of a sperm protein previously mistaken for a creatine kinase isoform was needed to anchor functional studies; sequencing defined it as the testis HSP70 chaperone HSPA2 and tied its absence to failed sperm-zona binding.

    Evidence Amino acid sequencing, immunocytochemistry, and immunoblotting in human sperm

    PMID:10952940

    Open questions at the time
    • Did not define the molecular partners mediating zona binding
    • Did not establish chaperone substrates
  2. 2006 High

    Whether HSPA2 had a direct biochemical role in spermatid genome condensation was unknown; proteomics placed it in transition-protein complexes, identifying it as the first chaperone for TP1/TP2.

    Evidence Global proteomics and protein-protein interaction validation in mouse condensing spermatids

    PMID:17035236

    Open questions at the time
    • Did not resolve whether HSPA2 folds or refolds transition proteins directly
    • No structural detail of the complex
  3. 2008 High

    The basis of HSPA2 protein stability in germ cells was unexplained despite known infertility phenotypes; Bat3/BAG6 loss showed HSPA2 is degraded by the proteasome absent a stabilizing partner, linking its turnover to meiotic survival.

    Evidence Bat3 knockout mouse with proteasome-inhibitor rescue and meiotic marker analysis

    PMID:18678708

    Open questions at the time
    • Did not identify the E3 ligase acting on HSPA2 in germ cells
    • Mechanism of BAG6-mediated stabilization not resolved
  4. 2008 Medium

    Whether HSPA2 functions as a stress chaperone outside germ cells was untested; stress-induced redistribution to nucleoli and centrosomes in cancer cells indicated a proteotoxic-stress role.

    Evidence Immunofluorescence and fluorescent-fusion imaging in NSCLC cell lines under heat shock

    PMID:18452162

    Open questions at the time
    • Did not identify client proteins protected under stress
    • Functional consequence of centrosomal localization unknown
  5. 2009 High

    How HSPA2 controls meiotic cell-cycle timing was unclear; the tNASP-HSPA2-CDC2 complex with histone-stimulated ATPase activity was shown to gate the G2→M transition by sequestering CDC2 from cyclin B1.

    Evidence Co-IP, ATPase and kinase assays, and overexpression in primary spermatocytes

    PMID:19553603

    Open questions at the time
    • Did not establish in vivo necessity of the complex for meiotic entry
    • Stoichiometry and regulation of CDC2 release unresolved
  6. 2009 Medium

    The composition of the spermatid genome-reorganizing machinery was incomplete; PARP1/PARP2 were shown to bind and poly(ADP-ribosyl)ate HSPA2 within a TP2-containing complex, integrating chromatin remodeling with chaperone function.

    Evidence In vitro binding assays, immunohistochemistry, electron microscopy, and Parp2-deficient mice

    PMID:19607827

    Open questions at the time
    • Functional consequence of HSPA2 PARylation not defined
    • In vitro interactions not validated by reciprocal endogenous pulldown
  7. 2012 High

    The surface machinery by which HSPA2 enables egg recognition was undefined; MS identified HSPA2-SPAM1-ARSA multimeric complexes whose depletion abolishes sperm-zona binding.

    Evidence Label-free MS, Western blot, and complex isolation from human spermatozoa with loss-of-function correlation

    PMID:23209833

    Open questions at the time
    • Did not establish direct binding geometry within the complex
    • Whether HSPA2 chaperones SPAM1/ARSA folding unresolved
  8. 2012 Medium

    How a static surface complex becomes competent for egg interaction was unknown; capacitation was shown to drive PKA/tyrosine-kinase- and membrane-fluidity-dependent translocation of the complex to the apical head.

    Evidence Flow cytometry, immunofluorescence, and pharmacological inhibition in human sperm

    PMID:23247813

    Open questions at the time
    • Direct signaling link between PKA/tyrosine kinases and complex movement not mapped
    • Single-lab observation
  9. 2012 Medium

    Whether HSPA2 alone confers somatic cytoprotection was untested; ectopic expression in HSPA2-null fibroblasts conferred resistance to proteasome-inhibitor-induced apoptosis.

    Evidence Stable retroviral overexpression and survival/apoptosis assays in V79 cells

    PMID:22397456

    Open questions at the time
    • Did not identify protected clients
    • Single phenotypic readout
  10. 2015 Medium

    Transcriptional control of HSPA2 in somatic contexts was unknown; HIF-1α was shown to bind the HSPA2 promoter and exert context-dependent (repressive in keratinocytes, activating in HeLa) regulation.

    Evidence ChIP, reporter assays, RNAi, and HIF-1α overexpression in two cell types

    PMID:26164067

    Open questions at the time
    • Basis of cell-type-dependent directionality not explained
    • In vivo relevance untested
  11. 2015 Medium

    Whether HSPA2 stability is regulated in human germ cells was unresolved; BAG6 was shown to stably bind HSPA2 and co-translocate during capacitation, with concomitant deficiency in infertile men.

    Evidence Co-immunofluorescence, Co-IP, and Western blot in human germ cells and patient spermatozoa

    PMID:26153132

    Open questions at the time
    • Causality between BAG6 loss and HSPA2 loss not established in humans
    • Single-lab patient correlation
  12. 2017 Medium

    A function for HSPA2 in epithelial homeostasis was unknown; silencing in keratinocytes showed it maintains the undifferentiated basal state and restrains premature terminal differentiation.

    Evidence shRNA knockdown, clonogenic/adhesion assays, and 3D reconstructed epidermis

    PMID:28786487

    Open questions at the time
    • Molecular targets of HSPA2 in keratinocyte differentiation not identified
    • Single-lab
  13. 2019 High

    The E3 ligase governing HSPA2 turnover and its cancer relevance were unknown; RNF144A was identified as the first HSPA2 E3 ligase, with HSPA2 degradation mediating its tumor-suppressive effects.

    Evidence Quantitative proteomics, Co-IP, ubiquitination assays, active-site mutagenesis, rescue, and in vivo tumor models

    PMID:31406303

    Open questions at the time
    • Ubiquitination site on HSPA2 not mapped
    • Whether RNF144A acts on HSPA2 in germ cells untested
  14. 2019 Medium

    The downstream pathways through which HSPA2 supports tumor cell proliferation were unclear; knockdown induced G1/S arrest via ERK1/2 activation and IRE1α/PERK ER stress.

    Evidence siRNA knockdown, cell-cycle flow cytometry, Western blot, and rescue in lung adenocarcinoma lines

    PMID:31807522

    Open questions at the time
    • Direct chaperone clients linking HSPA2 to ERK/ER stress not identified
    • Single-lab
  15. 2022 Medium

    A somatic stabilizer of HSPA2 and a metabolic role were unknown; USP20 was shown to deubiquitinate and stabilize HSPA2, with the axis promoting lipid accumulation and being downregulated after sleeve gastrectomy.

    Evidence Co-IP, MS, and in vitro lipid-accumulation assays with knockdown/overexpression

    PMID:36636478

    Open questions at the time
    • Mechanism by which HSPA2 promotes lipid accumulation not defined
    • USP20 deubiquitination of HSPA2 not site-mapped
  16. 2025 Medium

    A role for HSPA2 in early embryogenesis was unknown; asymmetric HSPA2 expression and CARM1 interaction were shown to bias 2-cell blastomere progeny toward ICM fate.

    Evidence Blastomere-specific knockdown/overexpression, lineage tracking, and Co-IP with CARM1 in mouse embryos

    PMID:40063400

    Open questions at the time
    • How HSPA2 modulates CARM1 activity not resolved
    • Single-lab
  17. 2025 Medium

    Whether HSPA2 controls epidermal inflammation was unknown; knockout impaired granular-layer development and increased pro-inflammatory cytokine/chemokine secretion and interferon-stimulated genes via an HSPA1-dependent network.

    Evidence CRISPR/shRNA knockout, transcriptomics, ELISA, and HSPA1 knockdown rescue in 3D epidermis

    PMID:40287440

    Open questions at the time
    • Mechanism linking HSPA2 loss to extracellular HSPA1 release unclear
    • Single-lab
  18. 2026 High

    Whether HSPA2 modulates innate immunity was unknown; it was shown to bind TBK1 and competitively block HERC5-mediated K63 ubiquitination at K608, suppressing IRF3 activation and type I interferon production.

    Evidence Hspa2-deficient mice, competition Co-IP, site-specific ubiquitination assays, and IRF3 translocation assays

    PMID:41934636

    Open questions at the time
    • Whether chaperone ATPase activity is required for TBK1 binding untested
    • Physiological trigger regulating HSPA2-TBK1 interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How post-translational modifications (lysine acetylation, PARylation) and disease contexts such as Parkinson's-associated α-synuclein aggregation mechanistically tune HSPA2 chaperone function remains unresolved.
  • Acetylation finding is correlational with no writer/eraser identified [#18]
  • α-synuclein aggregation effect lacks in vivo mechanistic validation [#19]
  • No unified model linking HSPA2 PTMs to chaperone activity

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2
Partners
ARSABAG6CDC2RNF144ASPAM1TBK1TP2USP20
Complex memberships
HSPA2-SPAM1-ARSA sperm surface complexspermatid TP2-HSPA2-PARP1/PARP2 complextNASP-HSPA2-CDC2 complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 HSPA2 is present in the acrosomal domain of human spermatozoa as a major component of 5 large molecular mass complexes; the dominant complex contains HSPA2 in close association with sperm adhesion molecule 1 (SPAM1) and arylsulfatase A (ARSA), both implicated in sperm-egg interaction. Depletion of HSPA2 from the sperm proteome completely abrogates sperm-zona binding. Label-free mass spectrometry, Western blot, Co-immunoprecipitation/complex isolation PloS one High 23209833
2012 The HSPA2-SPAM1-ARSA multimeric complex undergoes a capacitation-associated translocation in human spermatozoa, repositioning ARSA to the apical sperm head region compatible with zona pellucida interaction. This relocation is abolished by exogenous cholesterol or inhibitors of PKA and tyrosine kinases, indicating dependence on membrane fluidity changes and capacitation-associated signal transduction. Flow cytometry, immunofluorescence, inhibitor experiments (cholesterol loading, PKA inhibitors, tyrosine kinase inhibitors) Molecular human reproduction Medium 23247813
2006 During post-meiotic spermiogenesis in mouse, HSPA2 acquires new functions and becomes tightly associated with the major spermatid DNA-packaging proteins, transition proteins 1 and 2 (TP1 and TP2), identifying HSPA2 as the first known transition protein chaperone involved in genome-condensing structure assembly in spermatids. Global proteomic approach (mass spectrometry) identifying HSPA2 in genome-organizing protein complexes of condensing spermatids; protein-protein interaction confirmation The Journal of biological chemistry High 17035236
2009 In primary spermatocytes, the linker histone chaperone tNASP binds HSPA2 on the synaptonemal complex, forming a larger complex that also contains linker histones and CDC2. Linker histone binding to tNASP significantly increases HSPA2 ATPase activity, and the tNASP-HSPA2-histone complex precludes CDC2/cyclin B1 complex formation, decreasing CDC2/cyclin B1 kinase activity and thereby regulating the G2→M transition in meiosis prophase I. Co-immunoprecipitation, ATPase activity assay, kinase activity assay, overexpression experiments in primary spermatocytes Biology of reproduction High 19553603
2008 Bat3/Scythe (BAG-family related protein) is required for stability of Hsp70-2/HspA2 in male germ cells. Targeted inactivation of Bat3 in mice causes polyubiquitylation and proteasomal degradation of Hsp70-2 protein despite normal transcript levels; inhibition of the proteasome restores Hsp70-2 protein levels. Loss of Hsp70-2 is associated with widespread meiotic germ cell apoptosis, abnormal synaptonemal complex dynamics, and complete male infertility. Knockout mouse model (Bat3 conditional inactivation), Western blot, proteasome inhibitor rescue experiment, immunofluorescence (SYCP3, γ-H2AX, Rad51) The Journal of cell biology High 18678708
2009 In spermatids, Parp2 interacts with both transition protein TP2 and the transition chaperone HSPA2 via in vitro protein-protein interaction; this interaction is partly mediated by poly(ADP-ribosyl)ation. Parp1 poly(ADP-ribosyl)ates HSPA2 (but binds HSPA2 only weakly), while Parp2 interacts strongly with TP2 and HSPA2. These proteins form a spermatid-specific complex (Parp1, Parp2, TP2, HSPA2) involved in genome reorganization during spermiogenesis. In vitro protein-protein interaction assays, immunohistochemistry, electron microscopy, Parp2-deficient mouse model Experimental cell research Medium 19607827
2019 The E3 ubiquitin ligase RNF144A interacts with HSPA2 and targets it for ubiquitination and proteasomal degradation. Ligase-activity-defective RNF144A mutants fail to induce HSPA2 ubiquitination/degradation and fail to suppress breast cancer cell proliferation, migration, and invasion. Ectopic HSPA2 expression rescues the tumor-suppressive effects of RNF144A, establishing RNF144A as the first identified E3 ubiquitin ligase for HSPA2 in cancer. Quantitative proteomics, Co-immunoprecipitation, ubiquitination assay, active-site mutagenesis of RNF144A, rescue overexpression, in vitro and in vivo tumor models Cell death and differentiation High 31406303
2015 BAG6 co-localizes and stably interacts with HSPA2 in human testicular germ cells and epididymal spermatozoa. BAG6 undergoes capacitation-associated relocation from the equatorial region to the anterior head region, paralleling HSPA2 redistribution. Infertile men with zona pellucida binding defects related to HSPA2 deficiency also show concomitant BAG6 deficiency, suggesting BAG6 is a key regulator of HSPA2 stability/function in human germ cells. Co-immunofluorescence, protein-protein interaction assays (co-immunoprecipitation), Western blot in infertile patient spermatozoa Molecular human reproduction Medium 26153132
2008 In cancer cells (NSCLC lines A549 and NCI-H1299) at physiological temperature, HSPA2 localizes primarily to the cytoplasm; upon heat shock, HSPA2 redistributes to the nucleus, nucleoli, and centrosomes, suggesting roles in protecting nucleoli and centrosome integrity under proteotoxic stress. Immunofluorescence with specific anti-HSPA2 antibody, transfection with HSPA2-EGFP and mRFP-HSPA2 fusion proteins, qRT-PCR Journal of cellular biochemistry Medium 18452162
2000 HSPA2 (previously identified as a putative creatine kinase M isoform in human sperm) was definitively identified as the testis-expressed 70-kDa heat shock protein chaperone by amino acid sequencing. It is localized by immunocytochemistry to spermatocytes (low levels), spermatids, and the tail of mature sperm. Immature spermatozoa lacking HSPA2 show cytoplasmic retention and failure of zona pellucida binding. Amino acid sequencing, immunocytochemistry, immunoblotting (1D and 2D SDS-PAGE), cross-absorption with mouse HSP70-2 antibody Biology of reproduction High 10952940
2012 HSPA2 overexpression in somatic V79 fibroblasts (which lack endogenous HSPA2) confers resistance to bortezomib-induced apoptosis and proteasome inhibitor-mediated cytotoxicity, demonstrating that HSPA2 can function as a cytoprotective chaperone against proteotoxic stress in somatic cells. Stable retroviral overexpression of HSPA2 in V79 cells, cell survival assays, apoptosis assays Biochemistry and cell biology Medium 22397456
2017 HSPA2 is expressed in basal epidermal keratinocytes and participates in maintaining them in an undifferentiated state. Lentiviral shRNA silencing of HSPA2 in HaCaT keratinocytes causes reduced clonogenic potential, impaired adhesiveness, and increased expression of terminal differentiation markers. In a 3D reconstructed human epidermis model, HSPA2 deficiency accelerates development of a filaggrin-positive layer, indicating premature terminal differentiation. Lentiviral shRNA knockdown, colony-forming assay, adhesion assay, 3D reconstructed human epidermis model, immunofluorescence for differentiation markers Journal of cellular physiology Medium 28786487
2015 HIF-1 exerts cell context-dependent regulation of the HSPA2 gene: in keratinocytes (HaCaT), HIF-1α binds the HSPA2 promoter (via a hypoxia-response element, HRE) and suppresses HSPA2 transcription under hypoxia, while RNAi-mediated HIF-1α repression increases HSPA2 transcription. Conversely, in HeLa cells, HIF-1α activity upregulates HSPA2 expression. In vitro gene reporter assay (transient transfection), chromatin immunoprecipitation (ChIP), RNAi knockdown of HIF-1α, stable HIF-1α overexpression Biochimica et biophysica acta Medium 26164067
2019 HSPA2 knockdown via siRNA in lung adenocarcinoma cell lines causes G1/S phase cell cycle arrest, which is attributable at least in part to phosphorylation/activation of the ERK1/2 pathway and activation of IRE1α/PERK-mediated endoplasmic reticulum stress. Rescue assay confirmed these mechanisms. siRNA knockdown, flow cytometry (cell cycle analysis), Western blot for ERK1/2 and ER stress markers, colony forming assay, MTT assay, rescue assay Annals of translational medicine Medium 31807522
2022 USP20 (a deubiquitinase) stabilizes HSPA2 via the ubiquitin-proteasome pathway; USP20 and HSPA2 interact as demonstrated by co-immunoprecipitation and mass spectrometry. Both USP20 and HSPA2 promote lipid accumulation in vitro, and the USP20-HSPA2 axis is downregulated following sleeve gastrectomy in diet-induced obese mice, correlating with improved lipid dysmetabolism. Co-immunoprecipitation, mass spectrometry, immunoprecipitation, immunofluorescence, immunoblotting, siRNA knockdown/overexpression in vitro lipid accumulation assays Frontiers in endocrinology Medium 36636478
2025 HSPA2 is asymmetrically expressed in late 2-cell stage mouse embryos. Knockdown of Hspa2 in one blastomere of 2-cell embryos directs its progeny predominantly toward the inner cell mass (ICM) fate. HSPA2 interacts with CARM1 (a chromatin modifier), and HSPA2 levels correlate with expression of ICM-associated genes, identifying HSPA2 as a regulator of the first cell-fate decision in mammalian embryos. Blastomere-specific knockdown, overexpression in 2-cell embryos, immunofluorescence, co-immunoprecipitation with CARM1, gene expression analysis eLife Medium 40063400
2026 HSPA2 negatively regulates type I interferon (IFN-I) production by binding to TBK1 and competing with the E3 ubiquitin ligase HERC5 for TBK1 binding, thereby blocking HERC5-dependent K63-linked ubiquitination of TBK1 at lysine 608 (K608). This prevents formation of TBK1-associated complexes and suppresses subsequent IRF3 dimerization and nuclear translocation, blocking IFN-I production. Validated in Hspa2-deficient mice and cellular models. Hspa2-deficient mouse model, cellular overexpression/knockdown, co-immunoprecipitation (HSPA2-TBK1 and HERC5-TBK1 competition assay), ubiquitination assay (K63-linked, K608 site), IRF3 nuclear translocation assay Cell reports High 41934636
2025 HSPA2 deficiency (knockout) in keratinocytes impairs granular layer development with reduced filaggrin and involucrin expression, structural abnormalities in the upper epidermal layer in reconstructed epidermis, and increased secretion of pro-inflammatory IL-6, CCL2, CCL8, CXCL1, CXCL6, and CXCL10. HSPA2 knockout also increases extracellular HSPA1 and expression of interferon-stimulated genes; knocking down HSPA1 in HSPA2-deficient cells decreased IL-6 and CCL5 secretion, revealing HSPA1 as part of the HSPA2-regulated network. CRISPR/shRNA knockout, 3D reconstructed human epidermis, transcriptomic analysis, ELISA for cytokines/chemokines, Western blot, HSPA1 knockdown rescue experiments Cell death & disease Medium 40287440
2025 HSPA2 is hypoacetylated and downregulated in spermatozoa from idiopathic infertile patients. Lysine acetylation of HSPA2 was detected by immunoprecipitation-coupled LC-MS/MS, and Western blot validation confirmed reduced acetylation and protein levels correlated with elevated 4-HNE (oxidative stress marker), suggesting that lysine acetylation modulates HSPA2 chaperone function in spermatozoa. Immunoprecipitation coupled LC-MS/MS, Western blot, STRING network analysis, IPA network analysis Cell stress & chaperones Low 40645439
2025 In a Parkinson's disease context, overexpression of HSPA2 in HEK293T cells increased α-synuclein aggregate formation, while HSPA2 knockdown reduced α-synuclein aggregate accumulation, indicating HSPA2 modulates α-synuclein aggregation. HSPA2 overexpression and knockdown in HEK293T cells, α-synuclein aggregation assay, MPTP mouse model expression analysis Molecular neurobiology Low 41264038

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition. PloS one 121 23209833
2000 Putative creatine kinase M-isoform in human sperm is identifiedas the 70-kilodalton heat shock protein HspA2. Biology of reproduction 115 10952940
2006 Post-meiotic shifts in HSPA2/HSP70.2 chaperone activity during mouse spermatogenesis. The Journal of biological chemistry 101 17035236
1994 Cloning, sequencing, and mapping of the human chromosome 14 heat shock protein gene (HSPA2). Genomics 86 7829106
2012 Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition. Molecular human reproduction 74 23247813
1999 Specific expression of heat shock protein HspA2 in human male germ cells. Molecular human reproduction 63 10587366
2014 Expression, function, and regulation of the testis-enriched heat shock HSPA2 gene in rodents and humans. Cell stress & chaperones 62 25344376
2015 The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition. Asian journal of andrology 60 25865850
2006 Expression of the HSPA2 gene in ejaculated spermatozoa from adolescents with and without varicocele. Fertility and sterility 58 17007855
2005 Effect of varicocelectomy on sperm creatine kinase, HspA2 chaperone protein (creatine kinase-M type), LDH, LDH-X, and lipid peroxidation product levels in infertile men with varicocele. Urology 53 16140088
2012 Evaluation of HSPA2 in fertile and infertile individuals. Andrologia 51 22670834
2021 Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease. Molecular psychiatry 49 34480088
2019 RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation of stability and oncogenic functions of HSPA2. Cell death and differentiation 49 31406303
2017 Heat Shock Protein A2 (HSPA2): Regulatory Roles in Germ Cell Development and Sperm Function. Advances in anatomy, embryology, and cell biology 49 28389751
2008 Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis. The Journal of cell biology 47 18678708
2000 Repression of hspA2 messenger RNA in human testes with abnormal spermatogenesis. Fertility and sterility 46 10856471
2015 Novel characterization of the HSPA2-stabilizing protein BAG6 in human spermatozoa. Molecular human reproduction 42 26153132
2011 Differential expression of HSPA1 and HSPA2 proteins in human tissues; tissue microarray-based immunohistochemical study. Histochemistry and cell biology 42 21373891
2009 Linker histones stimulate HSPA2 ATPase activity through NASP binding and inhibit CDC2/Cyclin B1 complex formation during meiosis in the mouse. Biology of reproduction 36 19553603
2008 The HspA2 protein localizes in nucleoli and centrosomes of heat shocked cancer cells. Journal of cellular biochemistry 35 18452162
2014 HSPA2 is expressed in human tumors and correlates with clinical features in non-small cell lung carcinoma patients. Anticancer research 33 24922646
2014 Evaluation of heat-shock protein A2 (HSPA2) in male rats before and after varicocele induction. Molecular reproduction and development 32 25043441
2019 Functional redundancy of HSPA1, HSPA2 and other HSPA proteins in non-small cell lung carcinoma (NSCLC); an implication for NSCLC treatment. Scientific reports 27 31591429
2019 The anti-oxidant roles of Taurine and Hypotaurine on acrosome integrity, HBA and HSPA2 of the human sperm during vitrification and post warming in two different temperature. Cryobiology 24 31330124
2019 Downregulation of HSPA2 inhibits proliferation via ERK1/2 pathway and endoplasmic reticular stress in lung adenocarcinoma. Annals of translational medicine 21 31807522
2014 Depression of HspA2 in human testis is associated with spermatogenic impairment and fertilization rate in ICSI treatment for azoospermic individuals. Journal of assisted reproduction and genetics 19 25308252
2021 Evaluation of seminal plasma HSPA2 protein as a biomarker of human spermatogenesis status. Reproductive biology 18 34959194
2015 Expression and clinical significance of HSPA2 in pancreatic ductal adenocarcinoma. Diagnostic pathology 18 25890028
2009 Parp2 is required for the differentiation of post-meiotic germ cells: identification of a spermatid-specific complex containing Parp1, Parp2, TP2 and HSPA2. Experimental cell research 18 19607827
2004 Semen characteristics after overnight shipping: preservation of sperm concentrations, HspA2 ratios, CK activity, cytoplasmic retention, chromatin maturity, DNA integrity, and sperm shape. Journal of andrology 18 15223848
2017 Novel role for the testis-enriched HSPA2 protein in regulating epidermal keratinocyte differentiation. Journal of cellular physiology 17 28786487
2014 Expression of HSPA2 in human hepatocellular carcinoma and its clinical significance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 25117073
2020 Human sperm chaperone HSPA2 distribution during in vitro capacitation. Journal of reproductive immunology 16 33246276
2012 HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced apoptosis. Biochemistry and cell biology = Biochimie et biologie cellulaire 15 22397456
2009 The expression pattern of the 70-kDa heat shock protein Hspa2 in mouse tissues. Histochemistry and cell biology 14 19462178
2007 The structural and functional analysis of the human HSPA2 gene promoter region. Acta biochimica Polonica 12 17369882
2016 Testis-enriched heat shock protein A2 (HSPA2): Adaptive advantages of the birds with internal testes over the mammals with testicular descent. Scientific reports 10 26733092
2020 HSPA2 Chaperone Contributes to the Maintenance of Epithelial Phenotype of Human Bronchial Epithelial Cells but Has Non-Essential Role in Supporting Malignant Features of Non-Small Cell Lung Carcinoma, MCF7, and HeLa Cancer Cells. Cancers 9 32987811
2020 Various Anti-HSPA2 Antibodies Yield Different Results in Studies on Cancer-Related Functions of Heat Shock Protein A2. International journal of molecular sciences 8 32560263
2015 Cell type-dependent modulation of the gene encoding heat shock protein HSPA2 by hypoxia-inducible factor HIF-1: Down-regulation in keratinocytes and up-regulation in HeLa cells. Biochimica et biophysica acta 8 26164067
2022 Molecular Chaperone HSPA2 Distribution During Hyaluronic Acid Selection in Human Sperm. Reproductive sciences (Thousand Oaks, Calif.) 7 35819578
2018 Assessing the potential of HSPA2 and ADAM2 as two biomarkers for human sperm selection. Human fertility (Cambridge, England) 7 30463455
2016 Seminal plasma HSPA2 mRNA content is associated with semen quality. Journal of assisted reproduction and genetics 7 27209630
2024 The diabetic myocardial transcriptome reveals Erbb3 and Hspa2 as a novel biomarkers of incident heart failure. Cardiovascular research 5 39180332
2021 Paternal factors in recurrent pregnancy loss: an insight through analysis of non-synonymous single-nucleotide polymorphism in human testis-specific chaperone HSPA2 gene. Environmental science and pollution research international 5 34845642
2025 HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines. Cell death & disease 4 40287440
2023 Resveratrol ameliorates spermatogenesis by increasing protamine 1, 2 and HSPA2 expression in experimental varicocele rat model. Revista internacional de andrologia 3 37437508
2025 LncRNA SERPINB9P1 Mitigates Cerebral Injury Induced by Oxygen‒Glucose Deprivation/Reoxygenation by Interacting with HSPA2. Molecular neurobiology 2 39798045
2025 The asymmetric expression of HSPA2 in blastomeres governs the first embryonic cell-fate decision. eLife 2 40063400
2022 Sleeve gastrectomy improves lipid dysmetabolism by downregulating the USP20-HSPA2 axis in diet-induced obese mice. Frontiers in endocrinology 2 36636478
2021 Upregulated HSPA2 predicts early relapse of pancreatic cancer after surgery. Gland surgery 2 34422585
2025 HSPA2 emerges as a key biomarker: Insights from global lysine acetylproteomic profiling in idiopathic male infertility. Cell stress & chaperones 1 40645439
2022 [Effects of Yishen Tongluo Prescription on the PI3K-Akt-MTOR pathway and the protein and mRNA expressions of CatSper-1 and HSPA2 in the testis tissue of oligoasthenospermia rats]. Zhonghua nan ke xue = National journal of andrology 1 37477484
2026 YTHDF2 promotes m6A-modified HSPA2 translation to restrict Newcastle Disease Virus. Veterinary microbiology 0 41793872
2026 HSPA2 modulates antiviral immunity by inhibiting TBK1 activation. Cell reports 0 41934636
2025 The Potential Roles of HSPA2 in Parkinson's Disease. Molecular neurobiology 0 41264038
2025 Coinfection with fowl adenovirus serotypes 1 and 4 (FAdV-1 and -4) enhances FAdV-4 replication through FAdV-1-mediated upregulation of HSPA2 expression. Virulence 0 41408149
1997 Molecular analysis of uterine leiomyomas using the probes D7S13(7q) and HSPA2(14q). Oncology reports 0 21590236

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