HSPA8
HSPA8, also known as HSC70, HSC71 and HSP73, is a constitutively expressed member of the heat shock protein 70 family. It acts as a molecular chaperone in protein folding, chaperone-mediated autophagy and clathrin-coated vesicle uncoating. Browse Assay Genie's current range of HSPA8 research reagents below, or read on for the biology behind the target.
HSPA8 is a molecular chaperone that protects the proteome from stress, folds and transports newly synthesised polypeptides, re-folds misfolded proteins and controls the targeting of proteins for degradation. It works through cycles of ATP binding, ATP hydrolysis and ADP release. In the ATP-bound form it has low affinity for substrates; hydrolysis to ADP causes a conformational change that raises substrate affinity, allowing repeated cycles of binding and release. Co-chaperones regulate these cycles: J-domain HSP40 proteins stimulate ATP hydrolysis, nucleotide exchange factors such as BAG1/2/3 promote substrate release, and TPR-domain proteins such as HOPX and STUB1 direct outcomes including folding or degradation.
The HSPA8 gene encodes a member of the heat shock protein 70 family, which includes both heat-inducible and constitutively expressed proteins. HSPA8 belongs to the constitutive group, known as heat-shock cognate proteins. Alternatively spliced transcript variants encoding different isoforms have been reported. Orthologues are annotated in mouse and rat (Hspa8). The protein is found in the cytoplasm, nucleolus, melanosome, cell membrane and lysosome membrane.
HSPA8 has several specialised roles. It recognises cytosolic proteins bearing a -KFERQ motif in chaperone-mediated autophagy and recruits them to LAMP2 on the lysosome surface for degradation. With LAMP2 it also supports MHC class II presentation of cytoplasmic antigens. It takes part in ER-associated degradation with J-domain co-chaperones and the E3 ligase STUB1, and delivers preproteins to the mitochondrial import receptor TOMM70. Recruited to clathrin-coated vesicles by DNAJC6, its ATPase activity drives vesicle uncoating. It is also a component of the PRP19-CDC5L spliceosome complex, binds bacterial lipopolysaccharide, and represses CITED1 coactivator activity on Smad-mediated transcription. Earlier names include heat shock 70kD protein 8 and the previous symbol HSPA10.
HSPA8 supports folding of nascent polypeptides and re-folding of misfolded proteins, making it central to protein quality control studies.
HSPA8 recognises -KFERQ motif proteins and targets them to LAMP2 at the lysosome, a selective degradation route studied in autophagy research.
Its ATPase activity uncoats clathrin-coated vesicles after recruitment by DNAJC6, linking HSPA8 to the transport of membrane components.
With LAMP2, HSPA8 facilitates MHC class II presentation of cytoplasmic antigens, and it binds LPS to mediate inflammatory responses.
HSPA8 is a constitutively expressed Hsp70-family chaperone. It binds nascent and misfolded proteins in ATP-regulated cycles to promote folding, re-folding or degradation. It also drives chaperone-mediated autophagy, uncoats clathrin-coated vesicles, aids mitochondrial protein import and contributes to spliceosome function.
HSPA8 is also called HSC70, HSC71 and HSP73, and UniProt names it heat shock cognate 71 kDa protein. Earlier names include heat shock 70kD protein 8, and HSPA10 is a previous symbol. NCBI notes that alternatively spliced transcript variants encode different isoforms.
Mouse and rat both carry an orthologous gene named Hspa8. HSPA8 belongs to the heat shock protein 70 family and is a heat-shock cognate member, expressed constitutively rather than heat-induced. Check the datasheet of any product for its validated reactivity.
Other Hsp70 family members and heat shock proteins involved in chaperone and proteostasis research.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P11142; product specifications from Assay Genie datasheets.