Gene Symbol: Hspa9
Description: heat shock protein family A member 9
Alias: Crp40, GRP-75, Hspa9a, PBP74, stress-70 protein, mitochondrial, 75 kDa glucose-regulated protein, GRP 75, catecholamine regulated protein 40, heat shock 70 kDa protein 9, heat shock 70kDa protein 9A, heat shock protein 9, heat shock protein, A, mortalin, mtHSP70, peptide-binding protein 74
Species: rat
Products:     Hspa9

Top Publications

  1. Bruschi S, West K, Crabb J, Gupta R, Stevens J. Mitochondrial HSP60 (P1 protein) and a HSP70-like protein (mortalin) are major targets for modification during S-(1,1,2,2-tetrafluoroethyl)-L-cysteine-induced nephrotoxicity. J Biol Chem. 1993;268:23157-61 pubmed
    ..and that P84 is identical, over 14 residues, to a recently isolated novel member of the HSP70 family known as mortalin. These studies indicate that mitochondrial heat shock proteins are major targets for modification by reactive ..
  2. Shan Y, Cortopassi G. Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-sulfur cluster assembly. Mitochondrion. 2016;26:94-103 pubmed publisher
    ..syndrome (MDS) is characterized by ineffective hematopoiesis, and the disease overlaps with the gene Hspa9/Mortalin in multiple ways: the HSPA9 locus maps to 5q31...
  3. Ishihara N, Mihara K. Identification of the protein import components of the rat mitochondrial inner membrane, rTIM17, rTIM23, and rTIM44. J Biochem. 1998;123:722-32 pubmed
    ..These assays thus demonstrated the 18.1, 21.9, and 45 kDa proteins to be the translocator components of the rat mitochondrial inner membrane and, therefore, the functional homologues of Tim17, Tim23, and Tim44, respectively. ..
  4. Zhang G, Han M, Wang X, Xiao A. GRP75 Involves in Retinal Ganglion Cell Apoptosis After Rat Optic Nerve Crush. J Mol Neurosci. 2015;56:422-30 pubmed publisher
    ..Based on our data, we speculated that GRP75 might play an important role in RGCs apoptosis following ONC. ..
  5. Yang L, Guo W, Zhang Q, Li H, Liu X, Yang Y, et al. Crosstalk between Raf/MEK/ERK and PI3K/AKT in suppression of Bax conformational change by Grp75 under glucose deprivation conditions. J Mol Biol. 2011;414:654-66 pubmed publisher
    ..glucose deprivation (GD)-induced cellular stress, the molecular chaperone glucose-regulated protein 75 (Grp75)/Mortalin/PBP74/mtHSP70 (hereafter termed "Grp75") plays an important role in the suppression of apoptosis by ..
  6. Shi M, Jin J, Wang Y, Beyer R, Kitsou E, Albin R, et al. Mortalin: a protein associated with progression of Parkinson disease?. J Neuropathol Exp Neurol. 2008;67:117-24 pubmed publisher
    ..Of those, mortalin, a mitochondrial protein, was decreased in the advanced PD cases and was further validated to be decreased using ..
  7. Webster T, Naylor D, Hartman D, Høj P, Hoogenraad N. cDNA cloning and efficient mitochondrial import of pre-mtHSP70 from rat liver. DNA Cell Biol. 1994;13:1213-20 pubmed
    ..1993; mortalin, Wadhwa et al., 1993a; CSA, Michikawa et al...
  8. Yang T, Kozopas K, Craig R. The intracellular distribution and pattern of expression of Mcl-1 overlap with, but are not identical to, those of Bcl-2. J Cell Biol. 1995;128:1173-84 pubmed
    ..A burst of expression of mcl-1, prominently associated with mitochondria, complements the continued expression of bcl-2 in ML-1 cells differentiating along the monocyte/macrophage pathway. ..
  9. Mizukoshi E, Suzuki M, Loupatov A, Uruno T, Hayashi H, Misono T, et al. Fibroblast growth factor-1 interacts with the glucose-regulated protein GRP75/mortalin. Biochem J. 1999;343 Pt 2:461-6 pubmed
    ..One of the isolated proteins was identified as the glucose-regulated protein GRP75/mortalin/PBP-74/mthsp70, a member of the hsp70 family of heat-shock proteins known to be involved in regulating glucose ..

More Information


  1. Li X, Xu M, Zhao X, Zhao J, Chen F, Yu W, et al. Proteomic analysis of synovial fibroblast-like synoviocytes from rheumatoid arthritis. Clin Exp Rheumatol. 2013;31:552-8 pubmed
    ..The differentially expressed proteins identified in RA synovial FLSs might be candidate RA-associated proteins and may prove to be promising diagnostic indicators or new therapeutic targets for RA. ..
  2. Severino V, Locker J, Ledda Columbano G, Columbano A, Parente A, Chambery A. Proteomic characterization of early changes induced by triiodothyronine in rat liver. J Proteome Res. 2011;10:3212-24 pubmed publisher
    ..In addition, altered expression levels of several mitochondrial proteins (e.g., Hspa9, Atp5b, Cps1, Glud1, Aldh2, Ak2, Acads) demonstrated the known increase of mitochondrial biogenesis mediated by T3...
  3. Chiasserini D, Tozzi A, de Iure A, Tantucci M, Susta F, Orvietani P, et al. Mortalin inhibition in experimental Parkinson's disease. Mov Disord. 2011;26:1639-47 pubmed publisher
    Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease...
  4. Jin J, Hulette C, Wang Y, Zhang T, Pan C, Wadhwa R, et al. Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Mol Cell Proteomics. 2006;5:1193-204 pubmed
    ..We confirmed that one of these, mortalin (mthsp70/GRP75, a mitochondrial stress protein), is substantially decreased in PD brains as well as in a cellular ..
  5. Lo J, Hayashi M, Woo Kim S, Tian B, Huang J, Fearns C, et al. Tid1, a cochaperone of the heat shock 70 protein and the mammalian counterpart of the Drosophila tumor suppressor l(2)tid, is critical for early embryonic development and cell survival. Mol Cell Biol. 2004;24:2226-36 pubmed
    ..We propose that Tid1 is critical for early mammalian development, most likely for its function in sustaining embryonic-cell survival, which requires its association with Hsp70. ..
  6. De Mena L, Coto E, Sánchez Ferrero E, Ribacoba R, Guisasola L, Salvador C, et al. Mutational screening of the mortalin gene (HSPA9) in Parkinson's disease. J Neural Transm (Vienna). 2009;116:1289-93 pubmed publisher
    b>Mortalin is a mitochondrial chaperone of the heat shock protein 70 family. Mortalin plays a central role in mitochondrial biogenesis through its capacity to direct the import of nuclear-encoded proteins into the mitochondria...
  7. Krishna S, Alfonso L, Thekkumkara T, Abbruscato T, Bhat G. Angiotensin II induces phosphorylation of glucose-regulated protein-75 in WB rat liver cells. Arch Biochem Biophys. 2007;457:16-28 pubmed
    ..The ability of Ang-II to induce GRP-75 phosphorylation suggests that it may play a role in the protection of cytoplasmic proteins from the damaging effect of oxidative stress known to be produced during Ang-II induced signaling. ..
  8. Mikula M, Dzwonek A, Karczmarski J, Rubel T, Dadlez M, Wyrwicz L, et al. Landscape of the hnRNP K protein-protein interactome. Proteomics. 2006;6:2395-406 pubmed
    ..These observations greatly expanded the view of the landscape of K protein-protein interaction and provide new opportunities to explore signal transduction and gene expression in several subcellular compartments. ..
  9. Burbulla L, Schelling C, Kato H, Rapaport D, Woitalla D, Schiesling C, et al. Dissecting the role of the mitochondrial chaperone mortalin in Parkinson's disease: functional impact of disease-related variants on mitochondrial homeostasis. Hum Mol Genet. 2010;19:4437-52 pubmed publisher
    The mitochondrial chaperone mortalin has been linked to neurodegeneration in Parkinson's disease (PD) based on reduced protein levels in affected brain regions of PD patients and its interaction with the PD-associated protein DJ-1...
  10. Chen T, Kambal A, Krysiak K, Walshauser M, Raju G, Tibbitts J, et al. Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in hematopoietic progenitors in mice. Blood. 2011;117:1530-9 pubmed publisher
    ..Mutagenesis screens in zebrafish and mice identified Hspa9 as a del(5q31.2) candidate gene that may contribute to MDS and AML pathogenesis, respectively...
  11. Lv L, Li J, Qiao H, Nie B, Lu P, Xue F, et al. Overexpression of GRP75 inhibits inflammation in a rat model of intracerebral hemorrhage. Mol Med Rep. 2017;15:1368-1372 pubmed publisher
    ..GRP75 may, therefore, represent a promising target in the treatment of ICH. ..
  12. Gabriele N, Pontoriero G, Thomas N, Shethwala S, Pristupa Z, Gabriele J. Knockdown of mortalin within the medial prefrontal cortex impairs normal sensorimotor gating. Synapse. 2010;64:808-13 pubmed publisher
    The 70-kDa mitochondrial heat shock protein, mortalin, is a ubiquitously expressed, multifunctional protein that is capable of binding the neurotransmitter, dopamine, within the brain...
  13. Osorio C, Sullivan P, He D, Mace B, Ervin J, Strittmatter W, et al. Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice. Neurobiol Aging. 2007;28:1853-62 pubmed
    b>Mortalin is a chaperone protein associated with cell survival, stress response, intracellular trafficking, control of cell proliferation, mitochondrial biogenesis, and cell fate determination...
  14. Lee J, Kim C, Simon D, Aminova L, Andreyev A, Kushnareva Y, et al. Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem. 2005;280:40398-401 pubmed
  15. Johannesen J, Pie A, Karlsen A, Larsen Z, Jensen A, Vissing H, et al. Is mortalin a candidate gene for T1DM ?. Autoimmunity. 2004;37:423-30 pubmed
    b>Mortalin has been found to be up-regulated by 2D-protein gel analysis in isolated rodent islets exposed to cytokines...
  16. Naylor D, Stines A, Hoogenraad N, Høj P. Evidence for the existence of distinct mammalian cytosolic, microsomal, and two mitochondrial GrpE-like proteins, the Co-chaperones of specific Hsp70 members. J Biol Chem. 1998;273:21169-77 pubmed
  17. Fujita M, Nagai Y, Sawada T, Heese K. Identification of rTid-1, the rat homologue of the drosophila tumor suppressor l(2)tid gene. Mol Cell Biochem. 2004;258:183-9 pubmed
    ..This finding points to a pivotal role of Tid-1 in the control of cellular survival. ..
  18. Schulz C, Schendzielorz A, Rehling P. Unlocking the presequence import pathway. Trends Cell Biol. 2015;25:265-75 pubmed publisher
    ..Here, we review recent advances in understanding of the mechanisms underlying protein transport along the presequence pathway. ..
  19. Akamizu T, Saji M, Kohn L. A microsequencing approach to identify proteins which appear to interact with thyrotropin in rat FRTL-5 thyroid cells. Biochem Biophys Res Commun. 1990;170:351-8 pubmed
  20. Chanson A, Sayd T, Rock E, Chambon C, Sante Lhoutellier V, Potier de Courcy G, et al. Proteomic analysis reveals changes in the liver protein pattern of rats exposed to dietary folate deficiency. J Nutr. 2005;135:2524-9 pubmed
    ..Decreased abundance was also observed for cofilin 1, a protein linked to tumorigenesis, and for the GRP 75 precursor and preproalbumin, both of which are responsive to oxidative stress and/or inflammation...
  21. Guo W, Yang L, Li H, Xie Z, Liu W, Zuo J. Glucose-regulated protein 75 overexpression attenuates ionizing radiation-mediated injury in PC12 cells by inducing the expression of topoisomerase II?. Mol Med Rep. 2012;6:1423-7 pubmed publisher
    Glucose-regulated protein 75 (Grp75), also known as mortalin/mthsp70/PBP74, is a member of the heat-shock protein 70 (HSP70) family. Grp75 is known to protect cells from stress-induced injury...
  22. Wadhwa R, Yaguchi T, Hasan M, Mitsui Y, Reddel R, Kaul S. Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res. 2002;274:246-53 pubmed
    Hsp70 family member mot-2/mthsp70/GRP75/PBP74 was shown to bind to the tumor suppressor protein p53...
  23. Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, et al. Parkin interacts with Ambra1 to induce mitophagy. J Neurosci. 2011;31:10249-61 pubmed publisher
    ..These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy. ..
  24. Wadhwa R, Yaguchi T, Hasan M, Taira K, Kaul S. Mortalin-MPD (mevalonate pyrophosphate decarboxylase) interactions and their role in control of cellular proliferation. Biochem Biophys Res Commun. 2003;302:735-42 pubmed
    b>Mortalin (mot-2/GRP75/PBP74/mthsp70) is a member of the hsp70 family of proteins and is differentially distributed in normal and immortal cells. It was shown to be involved in pathways to cell senescence and immortalization...
  25. Zhang B, van Adel B, Gabriele J, Duong M, Henry P, Ball A, et al. Expression of the 40 kDa catecholamine regulated protein in the normal and injured rat retina. J Chem Neuroanat. 2002;24:41-8 pubmed
    b>Catecholamine regulated protein 40 (CRP40) has been shown to be expressed in the central nervous system (CNS) of several mammalian species where it may function in a similar manner to members of the heat shock protein (HSP) family...
  26. Bertrand J, Tennoune N, Marion Letellier R, Goichon A, Chan P, Mbodji K, et al. Evaluation of ubiquitinated proteins by proteomics reveals the role of the ubiquitin proteasome system in the regulation of Grp75 and Grp78 chaperone proteins during intestinal inflammation. Proteomics. 2013;13:3284-92 pubmed publisher
    ..Further studies should lead to the identification of ubiquitin ligases responsible for Grp75 and Grp78 ubiquitination. ..
  27. Massa S, Longo F, Zuo J, Wang S, Chen J, Sharp F. Cloning of rat grp75, an hsp70-family member, and its expression in normal and ischemic brain. J Neurosci Res. 1995;40:807-19 pubmed
    ..It is also highly similar to two non-mitochondrial proteins; mortalin, a senescence-related gene product, and pbp74, a protein implicated in B-cell peptide processing...