From Wikipedia, the free encyclopedia
Jump to: navigation, search
Heat shock 70kDa protein 1-like
Protein HSPA1L PDB 1hjo.png
PDB rendering based on 1hjo.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols HSPA1L ; HSP70-1L; HSP70-HOM; HSP70T; hum70t
External IDs OMIM140559 MGI96231 HomoloGene135835 GeneCards: HSPA1L Gene
RNA expression pattern
PBB GE HSPA1L 210189 at tn.png
More reference expression data
Species Human Mouse
Entrez 3305 15482
Ensembl ENSG00000204390 ENSMUSG00000007033
UniProt P34931 P16627
RefSeq (mRNA) NM_005527 NM_013558
RefSeq (protein) NP_005518 NP_038586
Location (UCSC) Chr 6:
31.78 – 31.78 Mb
Chr 17:
34.97 – 34.98 Mb
PubMed search [1] [2]

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene.[1][2][3] As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins.[3][4] Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation.[4][5] It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.[4][5][6]


This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein.[3] In order to properly fold non-native proteins, this protein interacts with the hydrophobic peptide segments of proteins in an ATP-controlled fashion. Though the exact mechanism still remains unclear, there are at least two alternative modes of action: kinetic partitioning and local unfolding. In kinetic partitioning, Hsp70s repetitively bind and release substrates in cycles that maintain low concentrations of free substrate. This effectively prevents aggregation while allowing free molecules to fold to the native state. In local unfolding, the binding and release cycles induce localized unfolding in the substrate, which helps to overcome kinetic barriers for folding to the native state. Ultimately, its role in protein folding contributes to its function in signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation.[4][5]

In addition to the process of protein folding, transport and degradation, this Hsp70 member can preserve the function of mutant proteins. Nonetheless, effects of these mutations can still manifest when Hsp70 chaperones are overwhelmed during stress conditions.[4] Furthermore, this protein enhances antigen-specific tumor immunity by facilitating more efficient antigen presentation to cytotoxic T cells.[5]

Clinical significance[edit]

Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis-inducing agents such as tumor necrosis factor-α (TNFα), staurosporin, and doxorubicin. This role leads to its involvement in many pathological processes, such as oncogenesis, neurodegeneration, and senescence. In particular, overexpression of HSP72 has been linked to the development some cancers, such as hepatocellular carcinoma, gastric cancers, colonic tumors, breast cancers, and lung cancers, which led to its use as a prognostic marker for these cancers.[5] Elevated Hsp70 levels in tumor cells may increase malignancy and resistance to therapy by complexing, and hence, stabilizing, oncofetal proteins and products and transporting them into intracellular sites, thereby promoting tumor cell proliferation.[4][5] As a result, tumor vaccine strategies for Hsp70s have been highly successful in animal models and progressed to clinical trials.[5] One treatment, a Hsp72/AFP recombined vaccine, elicited robust protective immunity against AFP-expressing tumors in mice experiments. Therefore, the vaccine holds promise for treating hepatocellular carcinoma.[5] Alternatively, overexpression of Hsp70 can mitigate the effects of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s corea, and spinocerebellar ataxias, and aging and cell senescence, as observed in centenarians subjected to heat shock challenge.[4]

HSPA1L is also involved in Graft-versus-host disease (GVHD) and has potential to serve as a diagnostic/prognostic biomarker.[6]


  1. ^ Ito Y, Ando A, Ando H, Ando J, Saijoh Y, Inoko H et al. (Aug 1998). "Genomic structure of the spermatid-specific hsp70 homolog gene located in the class III region of the major histocompatibility complex of mouse and man". Journal of Biochemistry 124 (2): 347–53. doi:10.1093/oxfordjournals.jbchem.a022118. PMID 9685725. 
  2. ^ Ishihara M, Ohno S (Nov 1997). "Genetic influences on sarcoidosis". Eye. 11. 11 ( Pt 2) (2): 155–61. doi:10.1038/eye.1997.44. PMID 9349405. 
  3. ^ a b c "Entrez Gene: HSPA1L heat shock 70kDa protein 1-like". 
  4. ^ a b c d e f g Mayer MP, Bukau B (Mar 2005). "Hsp70 chaperones: cellular functions and molecular mechanism". Cellular and Molecular Life Sciences 62 (6). doi:10.1007/s00018-004-4464-6. PMC 2773841. PMID 15770419. 
  5. ^ a b c d e f g h Wang X, Wang Q, Lin H, Li S, Sun L, Yang Y (Feb 2013). "HSP72 and gp96 in gastroenterological cancers". Clinica Chimica Acta; International Journal of Clinical Chemistry 417. doi:10.1016/j.cca.2012.12.017. PMID 23266770. 
  6. ^ a b Atarod S, Turner B, Pearce KF, Ahmed SS, Norden J, Bogunia-Kubik K et al. (Feb 2015). "Elevated level of HSPA1L mRNA correlates with graft-versus-host disease". Transplant Immunology. doi:10.1016/j.trim.2015.02.002. PMID 25680846. 

Further reading[edit]

External links[edit]