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FLASH GENE
Symbol HSPB1 contributors: mct/pgu - updated : 09-05-2016
HGNC name heat shock 27kDa protein 1
HGNC id 5246
Corresponding disease
CMT2F Charcot-Marie-Tooth disease, axonal, type 2F
Location 7q11.23      Physical location : 75.931.874 - 75.933.613
Synonym name
  • heat shock protein beta-1
  • stress-responsive protein 27
  • estrogen-regulated 24 kDa protein
  • 28 kDa heat shock protein
  • Synonym symbol(s) HSP27, HSP25, HSP28, HMN2B, SRP27, DKFZp586P1322, HS.76067
    DNA
    TYPE functioning gene
    STRUCTURE 1.74 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 914 22.7 205 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon highly
    Endocrinepancreas   highly
    Reproductivefemale systemovary  highly
    Urinarybladder   highly
    Visualeyeanterior segmentcornea  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus involved in multimerization
  • C terminus with the alpha cristallin domain responsible for chaperone function
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Hspb1 (84.9pc)
    homolog to rattus Hspb1 (83.4pc)
    intraspecies homolog to estrogen receptor
    Homologene
    FAMILY
  • small heat shock protein (HSP20) family
  • Hsp20/alpha crystallin subfamily
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • translocates from the cytoplasm to the nucleus upon stress induction or heat shock
  • cytoplasmic in interphase cells
  • colocalized with mitotic spindle in mitotic cells
  • basic FUNCTION
  • heat induced inhibitor of eIF4F dependent mRNA translation
  • overexpression associated with regulation of gene expression in keratinocytes
  • protects hippocampal progenitor cells from glucocorticoid-induced apoptotic cell death
  • involved in stress resitance and actin organization
  • atheroprotective, possibly by competing for uptake of atherogenic lipids by macrophages or by attenuating inflammation
  • can modulate SP1-dependent transcriptional activity to promote neuronal protection
  • involved in stress resistance and actin organization
  • may acts as a SUMO-E3 ligase specific for SUMO-E2/3
  • mediator of repression of AR function by PRKD1
  • facilitates the palmitoylation and plasma membrane translocation of the three classes of sex steroid receptors
  • role for HSPB1 in the balance between tumor dormancy and tumor progression, mediated by tumor–vascular interactions
  • plays a role in the control of non-centrosomal MT formation
  • role of HSP27 in corneal epithelial wound healing can be epithelial cell apoptosis, as well as epithelial migration
  • may regulate the proliferation, actin reorganization, and the migration of vascular smooth muscle cells (VSMCs)
  • is a negative regulator of ferroptotic cancer cell death
  • essential role for HSPB1 in iron metabolism with important effects on ferroptosis-mediated cancer therapy
  • unphosphorylated HSPB1 associates with EIF4E in osteoblasts and suppresses the translation initiation process
  • molecular chaperone which modifies the structures and functions of other proteins in cells when they are exposed to various stresses, such as chemotherapy
  • CELLULAR PROCESS cell life, antiapoptosis
    nucleotide, transcription, regulation
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    text inhibition
    PATHWAY
    metabolism
    signaling
    a component
  • cap initiation complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding eIF4G end facilitating dissociation of cap initiation complexes
  • interacting with the transcription factor SP1
  • interacting with the TGFB1I1
  • is also a downstream target of VEGFA through VEGFR2 and the MAPK14 signaling pathways
  • associating with alpha and beta-tubulin, microtubules and CRYAB
  • interacting with HSPB8 and HSPBAP1
  • MAPKAPK5 is involved in HSPB1-controlled F-actin dynamics in response to activation of the cAMP-dependent protein kinase pathway
  • binding to the SUMO-E2-conjugating enzyme
  • binds to a motif in estrogen receptor alpha (ESR1) and promotes palmitoylation of the steroid receptors
  • facilitates the trafficking of endogenous ESR1 to the plasma membrane
  • unphosphorylated HSPB1 has an inhibitory effect on BGLAP synthesis, but has a stimulatory effect on mineralization, in osteoblasts
  • TCHP negatively affects cell growth, induces cell death and regulates the expression and activation levels of HSPB1
  • interaction between SMURF2 and HSPB1, which suggested that SMURF2 mediated ubiquitylation-dependent degradation of HSPB1
  • interaction of SH3KBP1 with MAP3K4 was increased during the late phase of TNFSF10 incubation, suggesting that sustained MAPK14 and HSPB1 phosphorylation protects cells by preventing further cell death
  • HSPB1 phosphorylation serves as a novel regulator in TNF-induced apoptosis, providing a new insight into the cytoprotective role of HSPB1 phosphorylation
  • nuclear localization of NLK was mediated through direct interaction with HSPB1 which further protected cancer cells from apoptosis
  • cardiac HMGB1 increases HSPB1 expression and attenuates cardiomyocyte apoptosis associated with doxorubicin-induced cardiomyopathy
  • TGFB1I1 and HSPB1, HSPB2 are effectors of NOX4 required for TGFB1-stimulated Focal adhesions (FAs) formation, adhesion strength and migration in vascular smooth muscle cell
  • EXOC3 is involved in the enhancement of cell migration and suppression of apoptosis through the activation of HSPB1, HSPB2 or MAPK14 phosphorylation
  • cell & other
    REGULATION
    induced by environmental stress and developmental changes
    Phosphorylated by MAP3K12 (MAP3K12 is sufficient by itself to induce HSPB1 phosphorylation, cell periphery localization, and redistribution to the insoluble protein fraction (cytoskeleton) in poorly differentiated keratinocytes) (
    Other up-regulated in response to enterovirus 71 infection
    phosphorylated in MCF-7 cells on exposure to protein kinase C activators and heat shock
    ASSOCIATED DISORDERS
    corresponding disease(s) CMT2F
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    constitutional     --low  
    in atherosclerotic plaques
    constitutional     --over  
    in acute coronary syndrome
    tumoral     --over  
    is increased in chroni pancreatitis and pancreatic carcinoma
    tumoral     --over  
    in angiogenic human breast cancer cells compared with nonangiogenic human breast cancer cells
    tumoral     --low  
    aberrant promoter hypermethylation of the HSPB1 gene may explain the reduced expression of HSPB1 noted in oral cancer cells
    Susceptibility
  • lower lymphocyte HSPB1 levels might be associated with an increased risk of lung cancer
  • Variant & Polymorphism
    Candidate gene
  • defects in these gene are cause of distal hereditary motor neuropathy
  • expression of HSPB1 is an accurate and independent predictive biomarker of aggressive disease with a poor clinical outcome in prostate cancer without ETS-gene rearrangement
  • potentail novel serum marker for the diagnosis of chronic obstructive pulmonary disease in the smoking population
  • altered expression of this protein in testes showing abnormal spermatogenesis may be related to the pathogenesis of male infertility
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting HSPB1 might offer a useful strategy in cancer treatment
    neurologyneurodegenerative 
    . PEP1-HSPB1 fusion protein may be a potential therapeutic agent for familial amyotrophic lateral sclerosis patients
    cancerdigestivecolon
    may be a clinical target in patients with 5-FU-resistant colon cancer
    cancer  
    target for interrupting signaling from membrane sex steroid receptors to tumor biology in hormone-responsive cancers
    ANIMAL & CELL MODELS
  • HspB1-deficient murine fibroblasts exhibit reduced entry into S phase and increased expression of cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1)