Molecular chaperone implicated in a wide variety of cellularprocesses, including protection of the proteome from stress, foldingand transport of newly synthesized polypeptides, activation ofproteolysis of misfolded proteins and the formation and dissociation ofprotein complexes. Plays a pivotal role in the protein quality controlsystem, ensuring the correct folding of proteins, the re-folding ofmisfolded proteins and controlling the targeting of proteins forsubsequent degradation. This is achievedthrough cycles of ATP binding, ATP hydrolysis and ADP release, mediatedby co-chaperones. The co-chaperoneshave been shown to not only regulate different steps of the ATPasecycle of HSP70, but they also have an individual specificity such thatone co-chaperone may promote folding of a substrate while another maypromote degradation. The affinity ofHSP70 for polypeptides is regulated by its nucleotide bound state. Inthe ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes aconformational change that increases its affinity for substrateproteins. HSP70 goes through repeated cycles of ATP hydrolysis andnucleotide exchange, which permits cycles of substrate binding andrelease. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), thenucleotide exchange factors (NEF) such as BAG1/2/3 (facilitateconversion of HSP70 from the ADP-bound to the ATP-bound state therebypromoting substrate release), and the TPR domain chaperones such asHOPX and STUB1. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that formsan integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assemblyas it contacts all other components of the core complex. Bindsbacterial lipopolysaccharide (LPS) and mediates LPS-inducedinflammatory response, including TNF secretion by monocytes. Participates in the ER-associateddegradation (ERAD) quality control pathway in conjunction with Jdomain-containing co-chaperones and the E3 ligase STUB1. Interacts with VGF-derived peptide TLQP-21. [1-10]

MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHWPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTAAAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVNHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVEKALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAPRGVPQIEVTFDIDANGILNVSAVDKSTGKENKITITNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFNMKATVEDEKLQGKINDEDKQKILDKCNEIINWLDKNQTAEKEEFEHQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD