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Last update 08 May 2025

HSPA9

Last update 08 May 2025

Basic Info

Synonyms

75 kDa glucose-regulated protein, GRP-75, GRP75

+ [12]

Introduction

Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). May play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Molecular adapter that regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity).

Drugs associated with HSPA9

SHetA2

Target

HSC70 x HSPA5 x HSPA9

Mechanism

HSC70 modulators [+2]

Active Org.

National Cancer Institute

Originator Org.

University of Oklahoma

Active Indication

Relapsed Solid Neoplasm

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

miR-200c(Fudan University)

Target

HSPA9

Mechanism

HSPA9 modulators

Active Org.

Fudan University

Originator Org.

Fudan University

Active Indication

Ovarian Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HSPA9 modulators(Hainan University)

Target

HSPA9

Mechanism

HSPA9 modulators

Active Org.

Hainan University

Originator Org.

Hainan University

Active Indication

Endometrial Carcinoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with HSPA9

NCT04928508

/ RecruitingPhase 1IIT

Phase 1 Trial of OK-1 (SHetA2) in Patients With Advanced or Recurrent Solid Tumors

The purpose of this research is to test the safety of the study drug (OK-1) and see what effects (good and bad) this drug has on patients with recurrent solid tumors.

Start Date27 Jul 2022

Sponsor / Collaborator

University of Oklahoma

[+1]

100 Clinical Results associated with HSPA9

100 Translational Medicine associated with HSPA9

0 Patents (Medical) associated with HSPA9

1,213

Literatures (Medical) associated with HSPA9

01 Aug 2025·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

HSPA8 and HSPA9: Two prognostic and therapeutic targets in breast, colon, and kidney cancers?

Review

Author: Zaltron, Elisabetta ; Ruzza, Alessia ; Vianello, Federica ; Celotti, Ilaria ; Severin, Filippo ; Scavezzon, Matteo ; Leanza, Luigi

The process of protein folding is important to ensure the efficient functioning of cells. The capacity of a protein to attain the three-dimensional native conformation can impact its structure and function. Errors in this process result in the accumulation of misfolded proteins, which can contribute to the development of various diseases, including cancer. To prevent the pileup of misfolded proteins, a number of control systems have been developed over the course of evolution. In this scenario, a pivotal function has been attributed to molecular chaperones and the ubiquitin-proteasome degradation system. In this paper, we concentrate on molecular chaperones, with a particular focus on a family of heat shock proteins (HSPs), to highlight any potential correlation between their expression and function and the development of cancer. Hence, we have collected data from various public databases regarding the HSP70 protein family. By employing mRNA expression signatures, prognostic value analysis, and differentially expressed gene ontology analysis, we have elucidated the tumor-specific role of two members of the HSP70 family, namely HSPA8 and HSPA9, in kidney renal clear cell carcinoma (KIRC), colon adenocarcinoma (COAD), and breast invasive carcinoma (BRCA). Our research shed light on the controversial and tumor-specific role of HSP70s. More in detail, we have identified HSPA8 and HSPA9 as potential prognostic and therapeutic targets involved in several biological processes leading to tumorigenesis, including nucleic acid maturation, cell signaling, vesicle trafficking, mitochondrial structure and function, and protein maturation.

01 Aug 2025·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Anxa10 and neuropathic pain: Insights into dysregulation of endoplasmic reticulum-mitochondria contact tethering complex and therapeutic potential

Article

Author: Yang, Yan-Ling ; Huang, Yun-Qiang ; Zhang, Kun-Long ; Wu, Fei-Fei ; Li, Shu-Jiao ; Wang, Ya-Yun ; Xia, Yu-Lu ; Zhu, Chang-Lei ; Liu, Bo-Zhi

The stability of membrane contact sites is critically dependent on Endoplasmic Reticulum mitochondria contact tethering complexes (EMCTCs), and dysregulation of these sites has been implicated in neuropathic diseases. In this study, we examined the role of Annexin A10 (Anxa10), a calcium-dependent protein, in neuropathic pain by investigating its influence on EMCTCs dysregulation. Using RNA sequencing, western blotting, and behavioral assays, we observed that spared nerve injury (SNI)-induced neuropathic pain significantly increased Anxa10 expression levels within the spinal dorsal horn (SDH) of mice. By employing cell-specific gene regulation via the Cre/loxp system, we utilized loxp-modified adeno-associated virus vectors to modulate Anxa10 expression in GAD2-Cre (inhibitory neurons), vGlut2-Cre (excitatory neurons), and Fos-Cre (activity-induced neurons) transgenic mice. Our results demonstrated that specific down-regulation of Anxa10 in excitatory neurons within the SDH alleviated neuropathic pain, whereas up-regulation of Anxa10, regardless of cell type, induced spontaneous pain in mice. Ultrastructural analysis of the endoplasmic reticulum (ER) and mitochondria, as well as double immunofluorescence staining, revealed that downregulation of Anxa10 mitigated the SNI-induced reduction in ER-mitochondrial distance. Additionally, it attenuated the SNI-induced upregulation of key components of EMCTCs, including IP3R, GRP75, and VDAC1, while preventing the SNI-induced downregulation of NCX3 expression. Furthermore, we formulated and validated the hypothesis that SGK1 and PI3K are positioned downstream of Anxa10. The up-regulation of Anxa10 compromised mitochondrial integrity and disrupted mitochondrial networks, ultimately leading to elevated oxidative stress. Collectively, these findings suggest that Anxa10 represents a promising therapeutic target for correcting EMCTCs dysregulation and mitigating neuropathic pain.

01 Jun 2025·Poultry Science

Consequences of in vitro exposure of chicken spermatozoa to the fungicide tebuconazole

Article

Author: Krywko-Valencia, Sandra ; Niżański, Wojciech ; Dupont, Joelle ; Partyka, Agnieszka ; Froment, Pascal ; Kowalczyk, Artur ; Płuciennik, Natalia ; Napierkowska, Skarlet ; Babapour, Azindokht

Tebuconazole (TEB), a fungicide that inhibits 14α-demethylase (CYP51) and disrupts ergosterol synthesis, poses environmental and health risks due to its persistence and low biodegradability. This study examined TEB in vitro effects on rooster spermatozoa. In Experiment 1, semen from 10 Green-legged Partridge roosters was incubated with TEB (0, 0.1, 1, 10, 100 µM) at 36°C for 3 hours. Sperm motility was analyzed with Computer-Aided Sperm Analysis (CASA) system, while flow cytometry assessed membrane integrity, mitochondrial function, acrosome status, chromatin structure, intracellular calcium, apoptosis, caspase activity, and lipid peroxidation after 1 and 3 hours of exposure. Malondialdehyde (MDA) concentration and total antioxidant capacity (T-OAC) were measured by spectrophotometer. In Experiment 2, calcium channel blockers (SNX 325, MRS-1845, Nifedipine, HC-056456) were tested under the same conditions, focusing on motility, membrane integrity, calcium levels, apoptosis, caspase activity, and lipid peroxidation. Results in experiment 1 have shown that TEB (0.1, 1, 10 µM) reduced sperm velocity (VAP) after 3 hours (P < 0.01) without altering other motility parameters. Acrosome status, intracellular calcium level, and lipid peroxidation decreased significantly at all TEB concentrations (P < 0.01). Early apoptosis declined at 1 µM TEB (P < 0.01), while mitochondrial activity and membrane integrity remained stable. MDA levels were reduced (P < 0.01), with no effect on T-OAC. In Experiment 2, calcium channel blockers decreased motility parameters (VAP, VCL, VSL, MOT, PROG) and intracellular calcium levels (P < 0.01), but did not affect membrane integrity. Lipid peroxidation and caspase activity declined (P < 0.01), with no impact on early apoptosis. These findings underscore TEB's role in inhibiting calcium channels, reducing ion influx, blocking calcium-driven pore formation, thereby preserving membrane integrity. This mechanism mitigates early apoptosis and lipid peroxidation in chicken sperm, shedding light on TEB's impact on motility, calcium balance, and cell function.

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HSPA9

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