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FLASH GENE

Symbol

HSPA1A

contributors: mct/pgu - updated : 02-03-2018

HGNC name	heat shock 70kDa protein 1A
HGNC id	5232

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	2.38 kb     1 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	binding site for FOXA1 transcription factor

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - HLA-B - G7 - HSPA1L - HSPA1B - (92kb) - HSPA1A - G8 -C2 C2 - cen
Text	see BAT@ ,LTA

regionally located

located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins

RNA

TRANSCRIPTS	type	messenger

text	may cause alternative splicing (Shimizu, 1999)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005345 1 - 2445 NP_005336 - 641 - 2005 15632129

EXPRESSION

Type

widely

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 Digestive intestine small intestine     highly   liver         Homo sapiens Endocrine adrenal gland         Homo sapiens   pancreas         Homo sapiens Lymphoid/Immune lymph node         Homo sapiens Nervous nerve       highly Reproductive female system breast       Homo sapiens Respiratory diaphragm         Homo sapiens   lung         Homo sapiens Urinary bladder         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     moderately Muscular striatum cardiac     Homo sapiens Muscular striatum skeletal     Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to rattus Hspa1b (96.4 pc)
	homolog to murine Hspa1b (95.2 pc)

Homologene

FAMILY

heat shock protein 70 family

CATEGORY

chaperone/stress

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus

basic FUNCTION	stabilizing preexistent proteins against aggregation
	mediating the folding of newly translated polypeptides in the cytosol as well as within organelles
	being able to recognize nonnative conformations of other proteins
	involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1
	blocking heat-induced apoptosis primarily by inhibiting Bax activation via the inhibition of stress-induced JNK activation
	acting upstream of the mitochondria to inhibit Fas-mediated apoptosis
	protecting GATA-1 from caspase-mediated proteolysis
	extracellular HSPBP1 and HSPA1A synergistically activate epidermal growth factor receptor
	playing an essential role in blocking inflammation and preventing insulin resistance in the context of genetic obesity or high-fat feeding
	has an essential role in ERBB2-induced tumorigenesis by regulating oncogene-induced senescence pathways
	role for the HSPA1A-PARK2 axis in the regulation of muscle insulin sensitivity

CELLULAR PROCESS	cell life, antiapoptosis
	protein, post translation, folding
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

text	response to unfolded protein

PATHWAY

metabolism

other

signaling

mRNA catabolism

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	SOX9 in chondrocytes and testicular cell lines
	interacting with TSC2
	interaction with HNRPD
	binding extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage
	binding to ERN1 enhances ERN1/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis
	HSPA1A stabilizes the WASF3 protein
	interacts with ATP2A1 to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with HSPA1A upregulation
	HSPA1A and CLEC14A interact on endothelial cells and this interaction regulates HSPA1A-induced angiogenesis
	HSPA1A and M6PR negatively regulated APP processing and Abeta production

cell & other

REGULATION

induced by

IL6 in skeletal muscle

inhibited by

quercetin

Other

up-regulated by FOXA1 in MCF7 breast cancer cell line

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   low expressed in gastric cancer constitutional     --over   in preeclampsia, and serum HSPA1A levels reflect systemic inflammation, oxidative stress and hepatocellular injury, but is significantly higher in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) than in severely preeclamptic patients without HELLP syndrome

Susceptibility

to coronary heart disease (CHD) to Meniere disease (MD)

Variant & Polymorphism other	+190CC genotype was associated with significantly higher risk of CHD
	frequency of having at least one 190C allele was significantly higher in the MD patients than the controls

Candidate gene
Marker
Therapy target	potential target for therapeutic treatment of obesity-induced insulin resistance
	System Type Disorder Pubmed neuromuscular myopathy   increasing the expression of HSPA1A in muscle has significant therapeutic potential for DMD and related conditions diabete     HSPA1A is a potential treatment to prevent Beta-cell mass decline in type 2 diabetic patients

ANIMAL & CELL MODELS