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HSPB1 (Heat-Shock 27 kDa Protein 1)

Written2009-03Ewa Laskowska, Dorota Kuczyńska-Wiśnik, Ewelina Matuszewska
Department of Biochemistry, University of Gdańsk, Kładki 24, 80-952 Gdańsk, Poland

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Alias (NCBI)HSP27
HGNC Alias symbHSP27
HGNC Previous nameheat shock 27kD protein 1
 heat shock 27kDa protein 1
LocusID (NCBI) 3315
Atlas_Id 40880
Location 7q11.23  [Link to chromosome band 7q11]
Location_base_pair Starts at 76302673 and ends at 76304292 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping HSPB1.png]
Local_order Genes flanking HSPB1 in centromere to telomere direction:
- MDH2 (mitochondrial malate dehydrogenase precursor)
- FLJ37078 (hypothetical protein LOC222183)
- YWHAG (tyrosine 3-monooxygenase/tryptophan)
- SRCRB40 (scavenger receptor cysteine-rich domain-containing group B protein precursor)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GJC1 (17q21.31)::HSPB1 (7q11.23)HSPB1 (7q11.23)::CAMKK2 (12q24.31)HSPB1 (7q11.23)::DDX17 (22q13.1)
HSPB1 (7q11.23)::EGR1 (5q31.2)HSPB1 (7q11.23)::FARP2 (2q37.3)HSPB1 (7q11.23)::HSPB1 (7q11.23)
HSPB1 (7q11.23)::KRT19 (17q21.2)HSPB1 (7q11.23)::MYO1B (2q32.3)HSPB1 (7q11.23)::OBSL1 (2q35)
HSPB1 (7q11.23)::RAPGEF5 (7p15.3)HSPB1 (7q11.23)::SHTN1 (10q25.3)HSPB1 (7q11.23)::STXBP1 (9q34.11)
HSPB1 (7q11.23)::UBE2M (19q13.43)HSPB1 (7q11.23)::WASF1 (6q21)RMRP (9p13.3)::HSPB1 (7q11.23)
SKP1 (5q31.1)::HSPB1 (7q11.23)TNNC2 (20q13.12)::HSPB1 (7q11.23)XPO5 (6p21.1)::HSPB1 (7q11.23)


Description The DNA sequence (1.69 Kb) contains 3 exons.
Transcription The transcript is 847 bp.
Pseudogene 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).


Note 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).
  Fig.1. HspB1 contains an N-terminal hydrophobic domain with a WDFP motif and an alpha-crystallin domain at residues Glu87-Pro168. The arrows indicate phosphorylation sites at serines 15, 78 and 82.
Description 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).
Expression 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).
Localisation 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: Parkinson's disease (Outeiro et al., 2006; Zourlidou et al., 2004), Alexander disease (Iwaki et al., 1993), Alzheimer's disease (Wilhelmus et al., 2006).
HspB1 was also detected as a surface membrane protein in some cancer cell types (Shin et al., 2003).
Function 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 p27Kip1, a cyclin-dependent kinase inhibitor. The HspB1- mediated proteolysis of p27Kip1 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 (O'Callaghan-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.
Homology 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).


  Fig2. Distribution of HSPB1 mutations in dHMN II and CMT2F patients.
dHMN: distal hereditary motor neuropathy, CMT: Charcot-Marie-Tooth type 2F disease, AD: autosomal dominant, AR: autosomal recessive.
Germinal 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.
Somatic Not known.

Implicated in

Entity Various cancers
Disease Increased levels of HspB1 have been detected in breast cancer, ovarian cancer, osteosarcomas, endometrial cancer and leukemias (Garrido et al., 2006; Ciocca and Calderwood, 2005). It was also reported that the pattern of HspB1 phosphorylation in tumor cells is different from that observed in nontransformed cells (Sarto et al., 2004; Tremolada et al., 2005).
Prognosis Overexpression of HspB1 correlates with poor prognosis in gastric, liver, prostate carcinoma and osteosarcomas (Glaessgen et al., 2008; Romani et al., 2007; Ciocca and Calderwood., 2005).
Increased IbpB1 expression is associated with a favorable prognosis in schistosomiasis-associated bladder carcinoma (El-Meghawry El-Kenawy et al., 2008), neuroblastoma (Zanini et al., 2007) and non-small cell lung carcinoma (Malusecka et al., 2008).
Patients with reduced HspB1 expression have poorer survival rates in oral squamous cell carcinoma (Lo Muzio et al., 2004) and ovarian carcinoma (Geisler et al., 2004).
Lower lymphocyte HspB1 level is associated with an increased risk of lung cancer (Wang et al., 2008).
Cytogenetics Not reported.
Hybrid/Mutated Gene Not known.
Abnormal Protein Not known.
Oncogenesis HspB1 is involved in oncogenesis and resistance to various anti-cancer therapies due to its cytoprotective activities. It is suggested that HspB1 plays a crucial function during metastasis formation (Zhao et al., 2007).
Strategies combining chemo- or radiotherapy with down-regulation of HspB1 have been proposed as effective anti-cancer treatments. The HspB1 knockdown by using small interfering RNA (siRNA) increases sensitivity of human epithelial cells to geldanamycin (McCollum et al., 2006) and pancreatic cancer cells to gemcitabine (Mori-Iwamoto et al., 2007). Blocking HspB1 by antisense RNA restores apoptosis induced by drugs in multiple myeloma cells (Chauhan et al., 2003) and human bladder cancer cells (Kamada et al., 2007). Various cancer cells transfected with antisense Hsp27 cDNA exhibits increased sensitivity to gamma-irradiation (Aloy et al., 2008). Down regulation of HspB1 by interferon C enhances drug sensitivity in oral squamous cell carcinoma (Yonekura et al., 2003). Kim et al. (2007) has demonstrated that a heptapeptide derived from protein kinase C delta (PKC delta)-V5 region sequesters HspB1 and sensitizes human cancer cells to irradiation and cisplatine.
Entity Charcot-Marie-Tooth type IIF disease (CMT-IIF) / distal hereditary motor neuropathy (dHMN)
Note A number of mutations in HspB1 has been identified that are associated with dHMNII or CMT2F (table of figure 2). The exact pathogenic mechanism of the HspB1 mutations is not yet understood. Expression of the mutant HspB1 (P182S) results in the formation of insoluble aggregates, affects assembly of neurofilament network and axonal transport in cortical neurons (Ackerley et al., 2006; Evgrafov et al., 2004; Zhai et al., 2007).
Disease CMT disease and dHMN belong to a clinically heterogeneous group of disorders characterized by progressive weakness and distal limb muscle atrophy due to nerve degeneration. The neuropathy of CMT affects both motor and sensory nerves. The phenotype of dHMN II resembles CMT2F, but sensory abnormalities are absent in dHMNII.
Entity Conformational disorders
Disease One of the characteristics of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amylotrophic lateral sclerosis (ALS) and Huntington disease is the formation of protein aggregates. HspB1 and other molecular chaperones are often detected as components of these aggregates.
Cerebral deposits of intracellular neurofibrylllary tangles and extracellular aggregates of amyloid beta peptide (Abeta) are the pathological hallmarks of Alzheimer's disease. Intracellular Lewy bodies associated with Parkinson's disease contain alpha-synuclein. In Huntington's disease (HD), a proteolytic fragment of the huntingtin protein that contains an expanded polyglutamine tract (polyQ), misfolds and forms aggregates. Rosenthal fibers of Alexander disease are cytoplasmic inclusions within astrocytes, which contain glial fibrillary acidic protein (GFAP) (Iwaki et al., 1993; Der Perng et al., 2006).
Numerous studies indicate that molecular chaperones associated with intra- and extracellular protein deposits, affects their production and toxicity.
It has been reported that HspB1 inhibits assembly of Abeta fibryls in vitro and reduces cerebrovascular toxicity of Abeta (Wilhelmus et al., 2006). HspB1 also inhibits GFAP polymerization (Der Perng et al., 2006) and toxicity induced by overexpression of alpha-synuclein or polyQ in neuronal cells (Outeiro et al., 2006; Zourlidou et al., 2004; Wyttenbach et al., 2002). It is proposed that the sequestering of HspB1 by Rosenthal fibers diminishes its function as an anti-apoptotic factor which in turn results in astrocytes degeneration (Mignot et al., 2004). Similarly, association of HspB1 with mutated Cu/Zn superoxide dismutase 1 (SOD1) may induce apoptosis (Okado-Matsumoto and Fridovich, 2002). Missense mutations in the gene coding for SOD1 cause familial cases of amyotrophic lateral sclerosis (ALS) characterized by the death of large motor neurons in the cerebral cortex and spinal cord (Rakhit and Chakrabartty, 2006).
Entity Williams syndrome
Note Stock et al. (2003) used FISH to map the HspB1 gene and they found that the band 7q11.23 also contains the site of the deletion associated with Williams sydrome (WS). The HSPB1 gene was deleted in three out of six WS patients examined in this study.
Disease Williams syndrome (WS, also known as Williams- Beuren syndrome, WBS) is a rare neurodevelopmental disorder characterized by multiple anomalies including: typical facial dysmorphisms (elfin face), congenital heart defects, infantile hypercalcemia, mental retardation and growth deficiency.


A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes.
Ackerley S, James PA, Kalli A, French S, Davies KE, Talbot K.
Hum Mol Genet. 2006 Jan 15;15(2):347-54. Epub 2005 Dec 20.
PMID 16368711
Protective role of Hsp27 protein against gamma radiation-induced apoptosis and radiosensitization effects of Hsp27 gene silencing in different human tumor cells.
Aloy MT, Hadchity E, Bionda C, Diaz-Latoud C, Claude L, Rousson R, Arrigo AP, Rodriguez-Lafrasse C.
Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):543-53. Epub 2007 Nov 5.
PMID 17980509
Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets.
Arrigo AP, Simon S, Gibert B, Kretz-Remy C, Nivon M, Czekalla A, Guillet D, Moulin M, Diaz-Latoud C, Vicart P.
FEBS Lett. 2007 Jul 31;581(19):3665-74. Epub 2007 Apr 24. (REVIEW)
PMID 17467701
Inhibition of cell death by a novel 16.2 kD heat shock protein predominantly via Hsp90 mediated lipid rafts stabilization and Akt activation pathway.
Bellyei S, Szigeti A, Boronkai A, Pozsgai E, Gomori E, Melegh B, Janaky T, Bognar Z, Hocsak E, Sumegi B, Gallyas F Jr.
Apoptosis. 2007 Jan;12(1):97-112.
PMID 17136496
Hsp27 negatively regulates cell death by interacting with cytochrome c.
Bruey JM, Ducasse C, Bonniaud P, Ravagnan L, Susin SA, Diaz-Latoud C, Gurbuxani S, Arrigo AP, Kroemer G, Solary E, Garrido C.
Nat Cell Biol. 2000 Sep;2(9):645-52.
PMID 10980706
Regulation of stress-induced intracellular sorting and chaperone function of Hsp27 (HspB1) in mammalian cells.
Bryantsev AL, Kurchashova SY, Golyshev SA, Polyakov VY, Wunderink HF, Kanon B, Budagova KR, Kabakov AE, Kampinga HH.
Biochem J. 2007 Nov 1;407(3):407-17.
PMID 17650072
Heterooligomeric complexes formed by human small heat shock proteins HspB1 (Hsp27) and HspB6 (Hsp20).
Bukach OV, Glukhova AE, Seit-Nebi AS, Gusev NB.
Biochim Biophys Acta. 2009 Mar;1794(3):486-95. Epub 2008 Dec 3.
PMID 19100870
Inhibition of Daxx-mediated apoptosis by heat shock protein 27.
Charette SJ, Lavoie JN, Lambert H, Landry J.
Mol Cell Biol. 2000 Oct;20(20):7602-12.
PMID 11003656
Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance.
Chauhan D, Li G, Hideshima T, Podar K, Mitsiades C, Mitsiades N, Catley L, Tai YT, Hayashi T, Shringarpure R, Burger R, Munshi N, Ohtake Y, Saxena S, Anderson KC.
Blood. 2003 Nov 1;102(9):3379-86. Epub 2003 Jul 10.
PMID 12855565
Distal hereditary motor neuropathy in Korean patients with a small heat shock protein 27 mutation.
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Exp Mol Med. 2008 Jun 30;40(3):304-12.
PMID 18587268
Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications.
Ciocca DR, Calderwood SK.
Cell Stress Chaperones. 2005 Summer;10(2):86-103.
PMID 16038406
Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c.
Concannon CG, Orrenius S, Samali A.
Gene Expr. 2001;9(4-5):195-201.
PMID 11444529
Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes.
Cuesta R, Laroia G, Schneider RJ.
Genes Dev. 2000 Jun 15;14(12):1460-70.
PMID 10859165
The Alexander disease-causing glial fibrillary acidic protein mutant, R416W, accumulates into Rosenthal fibers by a pathway that involves filament aggregation and the association of alpha B-crystallin and HSP27.
Der Perng M, Su M, Wen SF, Li R, Gibbon T, Prescott AR, Brenner M, Quinlan RA.
Am J Hum Genet. 2006 Aug;79(2):197-213. Epub 2006 Jun 12.
PMID 16826512
Genetic variant in the HSPB1 promoter region impairs the HSP27 stress response.
Dierick I, Irobi J, Janssens S, Theuns J, Lemmens R, Jacobs A, Corsmit E, Hersmus N, Van Den Bosch L, Robberecht W, De Jonghe P, Van Broeckhoven C, Timmerman V.
Hum Mutat. 2007 Aug;28(8):830.
PMID 17623484
Heat shock protein expression independently predicts survival outcome in schistosomiasis-associated urinary bladder cancer.
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Int J Biol Markers. 2008 Oct-Dec;23(4):214-8.
PMID 19199268
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Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V.
Nat Genet. 2004 Jun;36(6):602-6. Epub 2004 May 2.
PMID 15122254
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Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G.
Cell Cycle. 2006 Nov;5(22):2592-601. Epub 2006 Nov 15.
PMID 17106261
HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up.
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Eur J Gynaecol Oncol. 2004;25(2):165-8.
PMID 15032273
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APMIS. 2008 Oct;116(10):888-95.
PMID 19132982
Comparison of the small heat shock proteins alphaB-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle.
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Histochem Cell Biol. 2004 Nov;122(5):415-25. Epub 2004 Oct 12.
PMID 15480735
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PMID 16205709
Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism.
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J Biol Chem. 2008 May 2;283(18):12305-13. Epub 2008 Feb 25.
PMID 18299320
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PMID 3019832
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PMID 10777697
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Neurology. 2008 Nov 18;71(21):1660-8. Epub 2008 Oct 1.
PMID 18832141
A clinical phenotype of distal hereditary motor neuronopathy type II with a novel HSPB1 mutation.
Ikeda Y, Abe A, Ishida C, Takahashi K, Hayasaka K, Yamada M.
J Neurol Sci. 2009 Feb 15;277(1-2):9-12. Epub 2008 Oct 25.
PMID 18952241
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Iwaki T, Iwaki A, Tateishi J, Sakaki Y, Goldman JE.
Am J Pathol. 1993 Aug;143(2):487-95.
PMID 8393618
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Jakob U, Gaestel M, Engel K, Buchner J.
J Biol Chem. 1993 Jan 25;268(3):1517-20.
PMID 8093612
Subcorneal colocalization of the small heat shock protein, hsp27, with keratins and proteins of the cornified cell envelope.
Jonak C, Klosner G, Kokesch C, FOdinger D, HOnigsmann H, Trautinger F.
Br J Dermatol. 2002 Jul;147(1):13-9.
PMID 12100179
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Mol Cancer Ther. 2007 Jan;6(1):299-308. Epub 2007 Jan 11.
PMID 17218637
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Cell Stress Chaperones. 2003 Spring;8(1):53-61.
PMID 12820654
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J Biol Chem. 1994 Apr 15;269(15):11274-8.
PMID 8157658
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J Hum Genet. 2005;50(9):473-6. Epub 2005 Sep 10.
PMID 16155736
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PMID 17616692
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Landry J, Huot J.
Biochem Cell Biol. 1995 Sep-Oct;73(9-10):703-7. (REVIEW)
PMID 8714691
Heat shock protein 27 interacts with vimentin and prevents insolubilization of vimentin subunits induced by cadmium.
Lee JS, Zhang MH, Yun EK, Geum D, Kim K, Kim TH, Lim YS, Seo JS.
Exp Mol Med. 2005 Oct 31;37(5):427-35.
PMID 16264267
HSP 27 as possible prognostic factor in patients with oral squamous cell carcinoma.
Lo Muzio L, Leonardi R, Mariggio MA, Mignogna MD, Rubini C, Vinella A, Pannone G, Giannetti L, Serpico R, Testa NF, De Rosa G, Staibano S.
Histol Histopathol. 2004 Jan;19(1):119-28.
PMID 14702179
Stress proteins HSP27 and HSP70i predict survival in non-small cell lung carcinoma.
Malusecka E, Krzyzowska-Gruca S, Gawrychowski J, Fiszer-Kierzkowska A, Kolosza Z, Krawczyk Z.
Anticancer Res. 2008 Jan-Feb;28(1B):501-6.
PMID 18383892
Up-regulation of heat shock protein 27 induces resistance to 17-allylamino-demethoxygeldanamycin through a glutathione-mediated mechanism.
McCollum AK, Teneyck CJ, Sauer BM, Toft DO, Erlichman C.
Cancer Res. 2006 Nov 15;66(22):10967-75.
PMID 17108135
Alexander disease: putative mechanisms of an astrocytic encephalopathy.
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Cell Mol Life Sci. 2004 Feb;61(3):369-85. (REVIEW)
PMID 14770299
Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine.
Mori-Iwamoto S, Kuramitsu Y, Ryozawa S, Mikuria K, Fujimoto M, Maehara S, Maehara Y, Okita K, Nakamura K, Sakaida I.
Int J Oncol. 2007 Dec;31(6):1345-50.
PMID 17982661
Actin cytoskeleton and small heat shock proteins: how do they interact?
Mounier N, Arrigo AP.
Cell Stress Chaperones. 2002 Apr;7(2):167-76.
PMID 12380684
Hsp27 modulates p53 signaling and suppresses cellular senescence.
O'Callaghan-Sunol C, Gabai VL, Sherman MY.
Cancer Res. 2007 Dec 15;67(24):11779-88.
PMID 18089808
Amyotrophic lateral sclerosis: a proposed mechanism.
Okado-Matsumoto A, Fridovich I.
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):9010-4.
PMID 12060716
Small heat shock proteins protect against alpha-synuclein-induced toxicity and aggregation.
Outeiro TF, Klucken J, Strathearn KE, Liu F, Nguyen P, Rochet JC, Hyman BT, McLean PJ.
Biochem Biophys Res Commun. 2006 Dec 22;351(3):631-8. Epub 2006 Oct 26.
PMID 17081499
HSP27 favors ubiquitination and proteasomal degradation of p27Kip1 and helps S-phase re-entry in stressed cells.
Parcellier A, Brunet M, Schmitt E, Col E, Didelot C, Hammann A, Nakayama K, Nakayama KI, Khochbin S, Solary E, Garrido C.
FASEB J. 2006 Jun;20(8):1179-81. Epub 2006 Apr 26.
PMID 16641199
Hsp27 as a negative regulator of cytochrome C release.
Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S, Arrigo AP.
Mol Cell Biol. 2002 Feb;22(3):816-34.
PMID 11784858
Structure, folding, and misfolding of Cu,Zn superoxide dismutase in amyotrophic lateral sclerosis.
Rakhit R, Chakrabartty A.
Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):1025-37. Epub 2006 May 22.
PMID 16814528
Heat shock protein 27 controls apoptosis by regulating Akt activation.
Rane MJ, Pan Y, Singh S, Powell DW, Wu R, Cummins T, Chen Q, McLeish KR, Klein JB.
J Biol Chem. 2003 Jul 25;278(30):27828-35. Epub 2003 May 9.
PMID 12740362
Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation.
Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J, Gaestel M.
J Biol Chem. 1999 Jul 2;274(27):18947-56.
PMID 10383393
The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma.
Romani AA, Crafa P, Desenzani S, Graiani G, Lagrasta C, Sianesi M, Soliani P, Borghetti AF.
BMC Cancer. 2007 Dec 21;7:232.
PMID 18154639
Small heat shock proteins in smooth muscle.
Salinthone S, Tyagi M, Gerthoffer WT.
Pharmacol Ther. 2008 Jul;119(1):44-54. Epub 2008 May 16.
PMID 18579210
Expression of heat shock protein 27 in human renal cell carcinoma.
Sarto C, Valsecchi C, Magni F, Tremolada L, Arizzi C, Cordani N, Casellato S, Doro G, Favini P, Perego RA, Raimondo F, Ferrero S, Mocarelli P, Galli-Kienle M.
Proteomics. 2004 Aug;4(8):2252-60.
PMID 15274119
Mechanism of chaperone function in small heat shock proteins: dissociation of the HSP27 oligomer is required for recognition and binding of destabilized T4 lysozyme.
Shashidharamurthy R, Koteiche HA, Dong J, McHaourab HS.
J Biol Chem. 2005 Feb 18;280(7):5281-9. Epub 2004 Nov 12.
PMID 15542604
Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function.
Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM.
J Biol Chem. 2003 Feb 28;278(9):7607-16. Epub 2002 Dec 18.
PMID 12493773
Heat shock protein 27 gene: chromosomal and molecular location and relationship to Williams syndrome.
Stock AD, Spallone PA, Dennis TR, Netski D, Morris CA, Mervis CB, Hobart HH.
Am J Med Genet A. 2003 Jul 30;120A(3):320-5.
PMID 12838549
Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation.
Sugiyama Y, Suzuki A, Kishikawa M, Akutsu R, Hirose T, Waye MM, Tsui SK, Yoshida S, Ohno S.
J Biol Chem. 2000 Jan 14;275(2):1095-104.
PMID 10625651
The small heat shock proteins and their role in human disease.
Sun Y, MacRae TH.
FEBS J. 2005 Jun;272(11):2613-27.
PMID 15943797
Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease.
Tang B, Liu X, Zhao G, Luo W, Xia K, Pan Q, Cai F, Hu Z, Zhang C, Chen B, Zhang F, Shen L, Zhang R, Jiang H.
Arch Neurol. 2005 Aug;62(8):1201-7.
PMID 16087758
Characterization of heat shock protein 27 phosphorylation sites in renal cell carcinoma.
Tremolada L, Magni F, Valsecchi C, Sarto C, Mocarelli P, Perego R, Cordani N, Favini P, Galli Kienle M, Sanchez JC, Hochstrasser DF, Corthals GL.
Proteomics. 2005 Feb;5(3):788-95.
PMID 15682460
HSP27 regulates p53 transcriptional activity in doxorubicin-treated fibroblasts and cardiac H9c2 cells: p21 upregulation and G2/M phase cell cycle arrest.
Venkatakrishnan CD, Dunsmore K, Wong H, Roy S, Sen CK, Wani A, Zweier JL, Ilangovan G.
Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1736-44. Epub 2008 Feb 8.
PMID 18263706
Upregulation of HSP27 in a transgenic model of ALS.
Vleminckx V, Van Damme P, Goffin K, Delye H, Van Den Bosch L, Robberecht W.
J Neuropathol Exp Neurol. 2002 Nov;61(11):968-74.
PMID 12430713
The level of Hsp27 in lymphocytes is negatively associated with a higher risk of lung cancer.
Wang F, Feng M, Xu P, Xiao H, Niu P, Yang X, Bai Y, Peng Y, Yao P, Tan H, Tanguay RM, Wu T.
Cell Stress Chaperones. 2009 May;14(3):245-251. Epub 2008 Sep 18.
PMID 18800238
Specific association of small heat shock proteins with the pathological hallmarks of Alzheimer's disease brains.
Wilhelmus MM, Otte-Holler I, Wesseling P, de Waal RM, Boelens WC, Verbeek MM.
Neuropathol Appl Neurobiol. 2006 Apr;32(2):119-30.
PMID 16599941
Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin.
Wyttenbach A, Sauvageot O, Carmichael J, Diaz-Latoud C, Arrigo AP, Rubinsztein DC.
Hum Mol Genet. 2002 May 1;11(9):1137-51.
PMID 11978772
Interferon-gamma downregulates Hsp27 expression and suppresses the negative regulation of cell death in oral squamous cell carcinoma lines.
Yonekura N, Yokota S, Yonekura K, Dehari H, Arata S, Kohama G, Fujii N.
Cell Death Differ. 2003 Mar;10(3):313-22.
PMID 12700631
Proteomic identification of heat shock protein 27 as a differentiation and prognostic marker in neuroblastoma but not in Ewing's sarcoma.
Zanini C, Pulera F, Carta F, Giribaldi G, Mandili G, Maule MM, Forni M, Turrini F.
Virchows Arch. 2008 Feb;452(2):157-67. Epub 2007 Dec 8.
PMID 18066588
Heat shock protein 27 and alpha B-crystallin can form a complex, which dissociates by heat shock.
Zantema A, Verlaan-De Vries M, Maasdam D, Bol S, van der Eb A.
J Biol Chem. 1992 Jun 25;267(18):12936-41.
PMID 1618790
Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.
Zhai J, Lin H, Julien JP, Schlaepfer WW.
Hum Mol Genet. 2007 Dec 15;16(24):3103-16. Epub 2007 Sep 19.
PMID 17881652
Differential proteomic analysis of human colorectal carcinoma cell lines metastasis-associated proteins.
Zhao L, Liu L, Wang S, Zhang YF, Yu L, Ding YQ.
J Cancer Res Clin Oncol. 2007 Oct;133(10):771-82. Epub 2007 May 15.
PMID 17503081
HSP27 but not HSP70 has a potent protective effect against alpha-synuclein-induced cell death in mammalian neuronal cells.
Zourlidou A, Payne Smith MD, Latchman DS.
J Neurochem. 2004 Mar;88(6):1439-48.
PMID 15009645


This paper should be referenced as such :
Laskowska, E ; Dorota Kuczyńska-Wiśnik, D ; Matuszewska, E
HSPB1 (Heat-Shock 27 kDa Protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):130-136.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)HSPB1   5246
LRG (Locus Reference Genomic)LRG_248
Atlas Explorer : (Salamanque)HSPB1
Entrez_Gene (NCBI)HSPB1    heat shock protein family B (small) member 1
AliasesCMT2F; HEL-S-102; HMN2B; HS.76067; 
HSP27; HSP28; Hsp25; SRP27
GeneCards (Weizmann)HSPB1
Ensembl hg19 (Hinxton)ENSG00000106211 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000106211 [Gene_View]  ENSG00000106211 [Sequence]  chr7:76302673-76304292 [Contig_View]  HSPB1 [Vega]
ICGC DataPortalENSG00000106211
TCGA cBioPortalHSPB1
Genatlas (Paris)HSPB1
SOURCE (Princeton)HSPB1
Genetics Home Reference (NIH)HSPB1
Genomic and cartography
GoldenPath hg38 (UCSC)HSPB1  -     chr7:76302673-76304292 +  7q11.23   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HSPB1  -     7q11.23   [Description]    (hg19-Feb_2009)
GoldenPathHSPB1 - 7q11.23 [CytoView hg19]  HSPB1 - 7q11.23 [CytoView hg38]
Genome Data Viewer NCBIHSPB1 [Mapview hg19]  
OMIM602195   606595   608634   
Gene and transcription
Genbank (Entrez)AB020027 AF086135 AK296890 AK311446 AK311894
RefSeq transcript (Entrez)NM_001540
Consensus coding sequences : CCDS (NCBI)HSPB1
Gene ExpressionHSPB1 [ NCBI-GEO ]   HSPB1 [ EBI - ARRAY_EXPRESS ]   HSPB1 [ SEEK ]   HSPB1 [ MEM ]
Gene Expression Viewer (FireBrowse)HSPB1 [ Firebrowse - Broad ]
GenevisibleExpression of HSPB1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3315
GTEX Portal (Tissue expression)HSPB1
Human Protein AtlasENSG00000106211-HSPB1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP04792   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP04792  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP04792
Domaine pattern : Prosite (Expaxy)SHSP (PS01031)   
Domains : Interpro (EBI)A-crystallin/Hsp20_dom    ACD_HspB1    Alpha-crystallin/sHSP_animal    HSP20-like_chaperone   
Domain families : Pfam (Sanger)HSP20 (PF00011)   
Domain families : Pfam (NCBI)pfam00011   
Conserved Domain (NCBI)HSPB1
PDB (RSDB)2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
PDB Europe2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
PDB (PDBSum)2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
PDB (IMB)2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
Structural Biology KnowledgeBase2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
SCOP (Structural Classification of Proteins)2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
CATH (Classification of proteins structures)2N3J    3Q9P    3Q9Q    4MJH    6DV5    6GJH   
AlphaFold pdb e-kbP04792   
Human Protein Atlas [tissue]ENSG00000106211-HSPB1 [tissue]
Protein Interaction databases
IntAct (EBI)P04792
Ontologies - Pathways
Ontology : AmiGOproteasome complex  retina homeostasis  regulation of protein phosphorylation  RNA binding  protein kinase C binding  protein binding  extracellular space  nucleus  cytoplasm  cytoplasm  spindle  cytosol  cytoskeleton  plasma membrane  focal adhesion  regulation of translational initiation  negative regulation of protein kinase activity  response to unfolded protein  protein kinase C inhibitor activity  response to virus  regulation of autophagy  protein kinase binding  Z disc  positive regulation of interleukin-1 beta production  positive regulation of tumor necrosis factor production  intracellular signal transduction  cellular response to vascular endothelial growth factor stimulus  positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway  identical protein binding  identical protein binding  protein homodimerization activity  negative regulation of apoptotic process  regulation of I-kappaB kinase/NF-kappaB signaling  ubiquitin binding  positive regulation of blood vessel endothelial cell migration  protein folding chaperone  positive regulation of angiogenesis  chaperone-mediated protein folding  RNA polymerase II-specific DNA-binding transcription factor binding  extracellular exosome  platelet aggregation  anterograde axonal protein transport  negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway  axon cytoplasm  positive regulation of endothelial cell chemotaxis  
Ontology : EGO-EBIproteasome complex  retina homeostasis  regulation of protein phosphorylation  RNA binding  protein kinase C binding  protein binding  extracellular space  nucleus  cytoplasm  cytoplasm  spindle  cytosol  cytoskeleton  plasma membrane  focal adhesion  regulation of translational initiation  negative regulation of protein kinase activity  response to unfolded protein  protein kinase C inhibitor activity  response to virus  regulation of autophagy  protein kinase binding  Z disc  positive regulation of interleukin-1 beta production  positive regulation of tumor necrosis factor production  intracellular signal transduction  cellular response to vascular endothelial growth factor stimulus  positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway  identical protein binding  identical protein binding  protein homodimerization activity  negative regulation of apoptotic process  regulation of I-kappaB kinase/NF-kappaB signaling  ubiquitin binding  positive regulation of blood vessel endothelial cell migration  protein folding chaperone  positive regulation of angiogenesis  chaperone-mediated protein folding  RNA polymerase II-specific DNA-binding transcription factor binding  extracellular exosome  platelet aggregation  anterograde axonal protein transport  negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway  axon cytoplasm  positive regulation of endothelial cell chemotaxis  
REACTOMEP04792 [protein]
REACTOME PathwaysR-HSA-9009391 [pathway]   
NDEx NetworkHSPB1
Atlas of Cancer Signalling NetworkHSPB1
Wikipedia pathwaysHSPB1
Orthology - Evolution
GeneTree (enSembl)ENSG00000106211
Phylogenetic Trees/Animal Genes : TreeFamHSPB1
Homologs : HomoloGeneHSPB1
Homology/Alignments : Family Browser (UCSC)HSPB1
Gene fusions - Rearrangements
Fusion : MitelmanHSPB1::CAMKK2 [7q11.23/12q24.31]  
Fusion : MitelmanHSPB1::MYO1B [7q11.23/2q32.3]  
Fusion : QuiverHSPB1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHSPB1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HSPB1
Exome Variant ServerHSPB1
GNOMAD BrowserENSG00000106211
Varsome BrowserHSPB1
ACMGHSPB1 variants
Genomic Variants (DGV)HSPB1 [DGVbeta]
DECIPHERHSPB1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHSPB1 
ICGC Data PortalHSPB1 
TCGA Data PortalHSPB1 
Broad Tumor PortalHSPB1
OASIS PortalHSPB1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHSPB1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DHSPB1
Mutations and Diseases : HGMDHSPB1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)HSPB1
DoCM (Curated mutations)HSPB1
CIViC (Clinical Interpretations of Variants in Cancer)HSPB1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM602195    606595    608634   
Orphanet16915    14513   
Genetic Testing Registry HSPB1
NextProtP04792 [Medical]
Target ValidationHSPB1
Huge Navigator HSPB1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDHSPB1
Pharm GKB GenePA29511
Clinical trialHSPB1
DataMed IndexHSPB1
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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