Heat shock protein 90 alpha family class A member 1 (HSP90AA1)

HSP90AA1 encodes the human stress-inducible 90-kDa heat shock protein alpha (Hsp90A), which functions as a homodimer. It is complemented by the constitutively expressed paralog Hsp90B, sharing over 85% amino acid sequence identity. HSP90AA1 expression is initiated when cells experience proteotoxic stress. The protein operates as a molecular chaperone that promotes the maturation, structural maintenance, and proper regulation of specific target proteins. Its chaperoning ability is driven by structural rearrangements fueled by ATP hydrolysis. HSP90AA1 aids in the proper folding of specific target proteins through ATPase activity modulated by co-chaperones. Beyond its chaperone activity, HSP90AA1 plays critical roles in mitochondrial import by delivering preproteins to the mitochondrial import receptor TOMM70. It also functions in transcription regulation at multiple levels. HSP90AA1 has emerged as an intriguing cancer treatment target due to its interactions with numerous tumor-promoting proteins and its role in cellular stress adaptation. It is considered essential for malignant transformation and progression, with its extensive interactome associated with each hallmark of cancer. Interestingly, loss of HSP90AA1 has been associated with favorable outcomes after surgery in gastric cancer patients. The HSP90AA1 gene is located on chromosome 14q32.2 and encodes a protein that is 854 amino acids in length. It contains a highly conserved N-terminal domain, a charged domain, a middle domain involved in ATPase activity, a second charged domain, and a C-terminal domain

Other names

HSP90AHS90AHSP89HSP90HSP90NHSPC1HSPCAHSPCAL4FLJ31884Heat shock protein HSP 90-alpha

Inhibition of HSP90 chaperone function disrupts protein folding and quality control Targeting HSP90 affects multiple oncogenic proteins simultaneously Disruption of ATP-dependent structural rearrangements