Heat shock protein beta-1, ACD domain (IPR037876)
Short name: ACD_HspB1
Overlapping homologous superfamilies
- HSP20-like chaperone (IPR008978)
- Alpha crystallin/Hsp20 domain (IPR002068)
- Heat shock protein beta-1, ACD domain (IPR037876)
This entry represents the alpha crystallin domain (ACD) found in mammalian Hsp27 (also denoted HspB1 in human).
Small heat shock proteins (sHsps) are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits [PMID: 12475175, PMID: 16205709]. They are characterised by the presence of an alpha crystallin domain (ACD) [PMID: 11875128].
Hsp27 shows enhanced synthesis in response to stress. It is a molecular chaperone which interacts with a large number of different proteins. It is found in many types of human cells including breast, uterus, cervix, platelets and cancer cells. Hsp27 has diverse cellular functions including chaperoning, regulation of actin polymerization, keratinocyte differentiation, regulation of inflammatory pathways in keratinocytes, and protection from oxidative stress through modulating glutathione levels [PMID: 9325325, PMID: 20010861, PMID: 15706088, PMID: 18007587]. It is also a subunit of AUF1-containing protein complexes [PMID: 18573886]. Hsp27 has been linked to several transduction pathways regulating cellular functions including differentiation, cell growth, development, and apoptosis [PMID: 29037376]. Its activity can be regulated by phosphorylation. Its unphosphorylated state is a high molecular weight aggregated form (100-800kDa) composed of up to 24 subunits, which forms as a result of multiple interactions within the ACD, and is required for chaperone function and resistance to oxidative stress. Upon phosphorylation these large aggregates rapidly disassociate to smaller oligomers and chaperone activity is modified [PMID: 19411251].
High constitutive levels of Hsp27 have been detected in various cancer cells, in particular those of carcinoma origin [PMID: 17467701]. Over-expression of Hsp27 has a protective effect against various diseases-processes, including Huntington's disease [PMID: 17375066]. Mutations in Hsp27 have been associated with a form of distal hereditary motor neuropathy type II and Charcot-Marie-Tooth disease type 2 [PMID: 15122254].
- cd06475 (ACD_HspB1_like)