HSPA1B
Description
The HSPA1B (heat shock protein family A (Hsp70) member 1B) is a protein-coding gene located on chromosome 6.
Human gene HSPA1B is an intron-less gene which encodes for the heat shock protein HSP70-2, a member of the Hsp70 family of proteins. The gene is located in the major histocompatibility complex, on the short arm of chromosome 6, in a cluster with two paralogous genes, HSPA1A and HSPA1L. HSPA1A and HSPA1B produce nearly identical proteins because the few differences in their DNA sequences are almost exclusively synonymous substitutions or in the three prime untranslated region, heat shock 70kDa protein 1A, from HSPA1A, and heat shock 70kDa protein 1B, from HSPA1B. A third, more modified paralog to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two.
== Function == Heat shock 70kDa protein 1B is a chaperone protein, cooperating with other heat shock proteins and chaperone systems to maintain proteostasis by stabilizing the structural conformation of other proteins in the cell and protecting against stress-induced aggregation. Hsp70s have also been shown to bind and stabilize mRNA rich in adenine and uracil bases, independent of the occupational states of its other binding sites. This protein is deactivated by binding ATP, and activated by its dephosphorylation to ADP, which requires a potassium ion to facilitate the hydrolysis, or ATP-ADP exchange. Hsp70-2 specifically is developmentally expressed in male germ line cells during meiosis, where it is necessary for the formation of the complex between CDC2 and cyclin B1. It later becomes incorporated into the CatSper complex, a specialized calcium ion channel that enables spermatozoa motility.
== Clinical significance == Infertility has been observed in mice when HSA1B expression is disrupted, as CDC2 in unable to form the required heterodimer with cyclin B1 for the meiotic cell cycle to progress beyond S phase. Expression of heat shock protein 70kDa protein 2 in transformed tumor cells has been implicated in the rapid proliferation, metastasis, and inhibition of apoptosis in ovarian, bladder urothelial, and breast cancers. Patients with chronic hepatitis B or hepatitis C virus infection who harbor a HSPA1B-1267 single nucleotide polymorphism have a higher risk for developing hepatocellular carcinoma.
HSPA1B, also known as Heat shock 70 kDa protein 2 or Heat shock protein family A member 1B, is a molecular chaperone involved in various cellular processes, including protecting the proteome from stress, folding and transporting newly synthesized polypeptides, activating proteolysis of misfolded proteins, and forming and dissociating protein complexes. It plays a crucial role in the protein quality control system, ensuring correct protein folding, refolding misfolded proteins, and controlling protein targeting for degradation. This is achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, facilitated by co-chaperones. These co-chaperones regulate different steps of the ATPase cycle and exhibit individual specificity, with some promoting substrate folding while others promote degradation. The affinity for polypeptides is regulated by its nucleotide-bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolyzing ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It undergoes repeated cycles of ATP hydrolysis and nucleotide exchange, enabling cycles of substrate binding and release. The co-chaperones are categorized into three types: J-domain co-chaperones like HSP40s (stimulating ATPase hydrolysis by HSP70), nucleotide exchange factors (NEF) like BAG1/2/3 (facilitating conversion of HSP70 from the ADP-bound to the ATP-bound state, promoting substrate release), and TPR domain chaperones like HOPX and STUB1. It maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines its function in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX, assisting in chaperone-mediated protein refolding. Subsequently, it is deacetylated and binds to ubiquitin ligase STUB1, promoting ubiquitin-mediated protein degradation. It regulates centrosome integrity during mitosis and is required for maintaining a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle. It enhances STUB1-mediated SMAD3 ubiquitination and degradation, facilitating STUB1-mediated inhibition of TGF-beta signaling. It is essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation.
HSPA1B is also known as HSP70-1, HSP70-1B, HSP70-2, HSP70.1, HSP70.2, HSP72, HSPA1, HSX70.
