Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the HSPA1Agene.[5][6] 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.[5][6] In addition, Hsp72 also facilitates DNA repair.[7] Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation.[6][8] It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and inflammatory diseases such as Diabetes mellitus type 2 and rheumatoid arthritis.[9][10][8]

Available structures
PDB Ortholog search: PDBeRCSB
List of PDB id codes

1HJO, 1S3X, 1XQS, 2E88, 2E8A, 2LMG, 3A8Y, 3ATU, 3ATV, 3AY9, 3D2E, 3D2F, 3JXU, 3LOF, 4IO8, 4J8F, 4PO2, 4WV5, 4WV7, 5AR0, 5AQZ, 3Q49,%%s3D2E

Aliases HSPA1A, HEL-S-103, HSP70-1, HSP70-1A, HSP70I, HSP72, HSPA1, HSP70.1, heat shock protein family A (Hsp70) member 1A, HSP70.2, HSP70-2
External IDs OMIM: 140550MGI: 96244HomoloGene: 74294GeneCards: HSPA1A
Gene location (Human)
Chr. Chromosome 6 (human)[1]

Band 6p21.33 Start 31,815,543 bp[1]
End 31,817,946 bp[1]
Gene location (Mouse)
Chr. Chromosome 17 (mouse)[2]

Band 17 B1|17 18.51 cM Start 34,969,190 bp[2]
End 34,972,156 bp[2]
RNA expression pattern
Top expressed in
  • hypothalamus
  • anterior pituitary
  • trachea
  • trigeminal ganglion
  • bronchus
  • inferior ganglion of vagus nerve
  • seminal vesicula
  • spinal cord
  • renal medulla
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Species Human Mouse









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 6: 31.82 – 31.82 Mb Chr 17: 34.97 – 34.97 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

. . . HSPA1A . . .

This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 (Hsp70) family.[5] As a Hsp70 protein, it has a C-terminal protein substrate-binding domain and an N-terminalATP-binding domain.[11][12][13] The substrate-binding domain consists of two subdomains, a two-layered β-sandwich subdomain (SBDβ) and an α-helical subdomain (SBDα), which are connected by the loop Lα,β. SBDβ contains the peptide binding pocket while SBDα serves as a lid to cover the substrate binding cleft. The ATP binding domain consists of four subdomains split into two lobes by a central ATP/ADP binding pocket. The two terminal domains are linked together by a conserved region referred to as loop LL,1, which is critical for allosteric regulation. The unstructured region at the very end of the C-terminal is believed to be the docking site for co-chaperones.[13]

This protein is a member of the Hsp70 family. 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.[5] 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.[6] Ultimately, its role in protein folding contributes to its function in signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation.[6][8]

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.[6] Hsp72 also protects against DNA damage and participates in DNA repair, including base excision repair (BER) and nucleotide excision repair (NER).[7] Furthermore, this protein enhances antigen-specific tumor immunity by facilitating more efficient antigen presentation to cytotoxic T cells.[8] It is also involved in the ubiquitinproteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins.[5] Finally, Hsp72 can protect against disrupted metabolic homeostasis by inducing production of pro-inflammatory cytokines, tumor necrosis factor-α, interleukin 1β, and interleukin-6 in immune cells, thereby reducing inflammation and improving skeletal muscleoxidation.[9][14] Though at very low levels under normal conditions, HSP72 expression greatly increases under stress, effectively protecting cells from adverse effects in various pathological states.[15]

Along with its role in DNA repair, Hsp72 is also directly involved in caspase-dependent apoptosis by binding Apaf-1, thereby inhibiting procaspase-9 activation and release of cytochrome c.[11] Additionally, Hsp72 has been observed to inhibit apoptosis by preventing the release of SMAC/Diablo and binding XIAP to prevent its degradation.[12] Hsp72 is also involved in caspase-independent apoptosis, as it also binds AIFM1.[11]

. . . HSPA1A . . .

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. . . HSPA1A . . .