HSPA1B

This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction 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. It is also involved in the ubiquitin-proteasome 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. [provided by RefSeq, Jul 2008]

Heat Shock Protein Family A (Hsp70) Member 1B

Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may 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 hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:26865365, PubMed:24318877).

Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions 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 which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256).

Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183).

Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385).

Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).

(Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell.

ATP metabolic process Source: BHF-UCL
Cellular heat acclimation Source: UniProtKB
Cellular response to heat Source: UniProtKB
Cellular response to oxidative stress Source: ParkinsonsUK-UCL
Cellular response to steroid hormone stimulus Source: Reactome
Cellular response to unfolded protein Source: GO_Central
Chaperone cofactor-dependent protein refolding Source: GO_Central
mRNA catabolic process Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cell death Source: ParkinsonsUK-UCL
Negative regulation of cell growth Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
Negative regulation of inclusion body assembly Source: UniProtKB
Negative regulation of protein ubiquitination Source: ParkinsonsUK-UCL
Positive regulation of erythrocyte differentiation Source: UniProtKB
Positive regulation of gene expression Source: BHF-UCL
Positive regulation of interleukin-8 production Source: UniProtKB
Positive regulation of microtubule nucleation Source: UniProtKB
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: GO_Central
Positive regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Protein refolding Source: UniProtKB
Protein stabilization Source: UniProtKB
Regulation of mitotic spindle assembly Source: UniProtKB
Regulation of protein ubiquitination Source: BHF-UCL
Vesicle-mediated transport Source: GO_Central

Centrosome; Cytoplasm. Localized in cytoplasmic mRNP granules containing untranslated mRNAs.

In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress.