The DNA sequence (1.69 Kb) contains 3 exons.

The transcript is 847 bp.

Two pseudogenes have been identified:
- a processed retropseudogene lacking promoter elements on Xp11.23 (Hickey et al., 1996);
- a 5-truncated semiprocessed retropseudogene on 9q13-9q21 (Kappe et al., 2003).

HspB1 belongs to the ubiquitous family of small heat shock proteins (sHsps). sHsps are characterized by low molecular mass (12-30 kDa), a conserved C-terminal "a-crystallin" domain and oligomeric structure. sHsps bind denatured proteins and facilitate their refolding by the ATP-dependent molecular chaperones of the Hsp70 family (Haslbeck et al., 2005; Sun and MacRae, 2005).

HspB1 is a protein of 205 amino acids (22783 Da), which can be phosphorylated at serines 15, 78 and 82 by mitogen- activated protein kinases associated protein kinases (MAPKAP kinase 2, MAPKAP kinase 3). Various signals modulate HspB1 phosphorylation: growth factors, tumor necrosis factor, differentiating agents, heat and oxidative stress (Arrigo et al., 2007). HspB1 forms oligomers up to 1000 kDa, which are dynamic structures. Phosphorylation results in a decrease size of the oligomers (Kato et al., 1994; Rogalla et al., 1999). Dissociation of the oligomers is required for recognition of protein substrates (Shashidharamurthy et al., 2005). It has been reported that HspB1 forms heterooligomers with other sHsps: alphaB-crystallin (HspB5) and Hsp20 (HspB6) (Zantema et al., 1992; Sugiyama et al., 2000; Bukach et al., 2009).

Ubiquitous, produced constutively at high levels in heart and skeletal muscles (Sugiyama et al., 2000); overexpressed in response to a wide variety of physiological and environmental insults; produced at high levels in many tumors (Garrido et al., 2006). Increased expression of HspB1 in response to the aggregation of proteins specific for conformational diseases have been reported by several authors (Outeiro et al., 2006; Vleminckx et al., 2002).

Cytosol, nucleus. HspB1 has been identified as a component of the nuclear speckles, structures implied in RNA processing (Bryantsev et al., 2007).
HspB1 interacts with actin, intermediat filaments and microtubules (Landry and Huot, 1995; Mounier and Arrigo, 2002; Lee et al., 2005; Hino et al., 2000; Jonak et al., 2002). During ischemia in muscles, HspB1 is translocated from the cytosol to myofibryls (Golenhoffen et al., 2004).
HspB1 accumulates in protein aggregates associated with conformational diseases: Parkinsons disease (Outeiro et al., 2006; Zourlidou et al., 2004), Alexander disease (Iwaki et al., 1993), Alzheimers disease (Wilhelmus et al., 2006).
HspB1 was also detected as a surface membrane protein in some cancer cell types (Shin et al., 2003).

HspB1 acts as an ATP-independent molecular chaperone and prevents irreversible aggregation of bound substrates in vitro (Jakob et al., 1993).
HspB1 is involved in the remodeling of cytoskeleton during embryogenesis and protection of the cytoskeleton in cells exposed to various stresses, particularly in the skeletal and cardiac muscles (Mounier and Arrigo, 2002; Sugiyama et al., 2000; Golenhofen et al., 2004; Salinthone et al., 2008). HspB1 phosphorylated by p38 MAP kinase is necessary for migration of vascular smooth muscle cells, neutrophils, fibroblasts and breast epithelial cells (Salinthone et al., 2008).
HspB1 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes (Cuesta et al., 2000).
HspB1 interacts with different proteins of the programmed cell death machinery and thereby blocks apoptosis at distinct key points. It has been demonstrated that HspB1 sequesters cytochrome C and thus, prevents assembly of the apoptosome (Bruey et al., 2000a; Concannon et al., 2001). The release of Smac/Diablo from mitochondria is also blocked by HspB1 (Chauhan et al., 2003). In addition, HspB1 inhibits activation of procaspase-3 by caspase 9 (Garrido et al., 1999; Concannon et al., 2001). HspB1 prevents translocation of pro-apoptotic Bid to mitochondria by stabilization of actin microfilaments (Paul et al., 2002). Havasi et al. (2008) demonstrated that HspB1 inhibits activation of pro-apoptotic Bax protein via a phosphatidylinositol 3-kinase-dependent mechanism. In the extrinsic pathway (receptor-mediated cell death) HspB1 prevents interaction of DAXX (death domain associated protein) with Fas death receptor and protein kinase Ask1 in caspase-independent pathway (Charette et al., 2000). It has been reported by Rane et al. (2003) that HspB1 controls apoptosis by binding cytoprotective protein kinase B (Akt). Anti-oxidant properties of HspB1 play an important function in the regulation of apoptosis. HspB1 maintain glutathione in its reduced form and decrease the amount of reactive oxygen species (ROS) produced in cells exposed to oxidative stress or tumor necrosis factor TNFalpha (Arrigo et al., 2007). HspB1 may indirectly affect apoptosis by promoting degradation of death regulatory proteins by ubiquitin-proteasome pathway. Under stress conditions HspB1 stimulates ubiquitination of I-kappaBalpha, an inhibitor of the anti-apoptotic transcription factor NF-kappaB, and p27^Kip1, a cyclin-dependent kinase inhibitor. The HspB1- mediated proteolysis of p27^Kip1 facilitates progression from Go/G1 to S-phase of the cell cycle (Parcellier et al., 2006).
In cancer cells HspB1 participates in oncogenesis and resistance to chemotherapy (see below). It has also been reported that expression of recombinant HspB1 at elevated levels leads to protection of human mammary epithelial cells from doxorubicin. The protection is associated with suppression of the doxorubicin-induced senescence, where HspB1 inhibits p53-mediated induction of p21 (OCallaghan-Sunol et al., 2007). However, Venkatakrishnan and co-workers (2008) demonstrated that HspB1 causes p21 upregulation and G2/M phase cell cycle arrest in doxorubicin-treated fibroblasts.

HspB1 shares homology trough the conserved alpha-crystallin domain with other members of the sHsps family. Eleven human sHsps have been identified so far: HspB1 (Hsp27) HspB2, HspB3, alphaA-crystallin (HspB4), alphaB-crystallin (HspB5), Hsp20 (HspB6), cvHsp (HspB7), HspB8 (H11), HspB9, HspB10 (ODF1) and Hsp16.2 (Kappe et al., 2003; Bellyei et al., 2007).

Mutations in the HSPB1 gene were found to cause distal hereditary motor neuropathy type II (dHMN II) or Charcot-Marie-Tooth disease type 2F (CMT2F). Five of the mutations are located in the alpha-crystallin domain (see figure 2).
Dierick and co-workers (2007) identified a HSPB1 promoter variant (c.-217T>C) in an ALS patient, which drastically impaired the HSPB1 heat shock response.

Not known.