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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine large intestine colon   highly Endocrine pancreas       highly Reproductive female system ovary     highly Urinary bladder       highly Visual eye anterior segment cornea

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer     targeting HSPB1 might offer a useful strategy in cancer treatment neurology neurodegenerative   . PEP1-HSPB1 fusion protein may be a potential therapeutic agent for familial amyotrophic lateral sclerosis patients cancer digestive colon 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)