HSPA1L
Description
The HSPA1L (heat shock protein family A (Hsp70) member 1 like) is a protein-coding gene located on chromosome 6.
HSPA1L, the gene encoding Heat shock 70 kDa protein 1L, is located on chromosome 6 and belongs to the heat shock protein 70 (Hsp70) family. As a chaperone protein, HSPA1L assists in the proper folding of newly translated and misfolded proteins, stabilizing or degrading mutant proteins. Its functions are critical in various biological processes, including signal transduction, apoptosis, protein homeostasis, cell growth, and differentiation. HSPA1L has been linked to various diseases, including cancer, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease. The protein is encoded by a gene located in the major histocompatibility complex class III region, clustered with two closely related genes that also encode isoforms of the 70kDa heat shock protein. HSPA1L shares 90% homology in its amino acid sequence with the isoforms HSPA1A and HSPA1B. As an Hsp70 protein, HSPA1L possesses a C-terminal protein substrate-binding domain and an N-terminal ATP-binding domain. The substrate-binding domain consists of two subdomains, a two-layered β-sandwich subdomain (SBDβ) and an α-helical subdomain (SBDα), connected by the loop Lα,β. SBDβ contains the peptide binding pocket, while SBDα acts as a lid covering the substrate binding cleft. The ATP-binding domain is composed of four subdomains, separated into two lobes by a central ATP/ADP binding pocket. The two terminal domains are linked by a conserved region called loop LL,1, essential for allosteric regulation.
HSPA1L, also known as Heat shock 70 kDa protein 1-like, is a molecular chaperone involved in various cellular processes, including protection against cellular stress, folding and transport of newly synthesized proteins, promoting the degradation of misfolded proteins, and regulating protein complex formation and dissociation. HSPA1L is crucial for protein quality control, ensuring correct protein folding, refolding misfolded proteins, and directing proteins for degradation. This function is achieved through cycles of ATP binding, hydrolysis, and ADP release, facilitated by co-chaperones. The affinity of HSPA1L for polypeptides is regulated by its nucleotide binding state. In the ATP-bound form, HSPA1L exhibits low affinity for substrate proteins. However, upon ATP hydrolysis to ADP, HSPA1L undergoes a conformational change leading to increased affinity for substrate proteins. These repeated cycles of ATP hydrolysis and nucleotide exchange enable cycles of substrate binding and release (PMID:26865365). HSPA1L also acts as a positive regulator of PRKN translocation to damaged mitochondria (PMID:24270810).
HSPA1L is also known as HSP70-1L, HSP70-HOM, HSP70T, hum70t.
