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FLASH GENE

Symbol

HSPD1

contributors: mct - updated : 28-03-2020

HGNC name	heat shock 60kDa protein 1 (chaperonin)
HGNC id	5261

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head
text	head to head with HSPE1
STRUCTURE	13.69 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	bidirectional promoter with a SP1 transcription factor binding site

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002156 12 - 2339 NP_002147 - 573 - 2019 31112866 NM_199440 12 - 2319 NP_955472 - 573 - 2019 31112866

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 Digestive stomach       highly Endocrine adrenal gland       highly Hearing/Equilibrium ear inner cochlea     Rattus norvegicus Nervous nerve       highly Respiratory lung       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Nervous glia Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	amnion cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

fourteen identical subunits with a structure of two stacked heptameric rings arranged around a 2-fold axis of symetry

HOMOLOGY

interspecies

homolog to murine Hsp60

Homologene

FAMILY

chaperonin (HSP60) family

CATEGORY

chaperone/stress

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,mitochondria,matrix
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,peroxisome
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
text	can accumulate in the cytosol in various pathological conditions, including cancer and chronic inflammatory diseases

basic FUNCTION	involved in mitochondrial protein import and macromolecular assembly
	molecular chaperone involved in folding and quality control of mitochondrial proteins (Hansen 2007)
	plays an essential role in assisting a large variety of newly synthesized proteins to reach their native forms by binding and facilitating their folding into native status inside a large central channel within each ring (Tsai 2008)
	stimulate the best known TREM2-dependent process, phagocytosis
	loss of HSPD1 signaling contributes to the glucocorticoid-induced enhancement of pro-apoptotic reactions, thereby accelerating osteoblast apoptosis and bone mass loss
	might be a factor underlying adipose tissue inflammation and obesity-associated metabolic disorders
	plays an essential role in malignant cell survival
	HSPD1/HSPE1 may be implicated in the folding of membrane proteins
	plays an essential role in protein homeostasis through mediating protein folding and assembly
	is a mediator of stress-induced vascular smooth muscle cell (VSMC) proliferation
	mediates microglial IL1B production by regulating NLRP3 inflammasome pathway
	may play an important role in auditory function
	major mitochondrial chaperone for maintaining mitochondrial proteostasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

major component of the chaperonins complex which weighs nearly a million Daltons and is composed of back-to-back rings of identical or closely related rotationally symmetric subunits (Tsai 2008)

INTERACTION

DNA

RNA

small molecule

protein	interacting with HSPA9 through N-terminal region of HSPA9
	(involvement in tumorigenesis, functional distinction in pathways involved in senescence)
	binding to YBX1 in the cytoplasm and acting as a regulator of polysome association and subellular distribution of YBX1 (Ohashi 2009)
	HSPD1 is a novel regulator of mitochondrial permeability transition, contributing to a cytoprotective chaperone network that antagonizes PPIF-dependent cell death in tumors
	OLR1 through binding to extracellular HSPD1 promotes microglia-mediated neuroinflammation
	LEP plays an important role in mitochondrial function and insulin sensitivity in the hypothalamus by regulating HSPD1
	HSPD1 and SOD2 proteins interact (SOD2 likely is a substrate of the HSPD1 folding machinery and under conditions of diminished availability of HSPD1, SOD2 is impaired in reaching the native state
	HSPD1 interacted with IRF3 and it contributed to the induction of IFNB1
	FUS interacts with a mitochondrial chaperonin, HSPD1, and FUS translocation to mitochondria is, at least in part, mediated by HSPD1
	is involved in the stimulation of VSMC migration, via TLR4 and ERK MAPK activation
	co-chaperone for HSPD1, which is involved in the mitochondrial protein-folding machinery
	showed pro-inflammatory properties in bronchial epithelial cells mediated by activation of TLR4-related molecules
	possesses a GTPase activity and mediates protein folding with HSPE1
	VSMC proliferation can be modulated via an HSPD1 dependent, cytosol localized mechanism that in part involves a stimulation of nuclear protein import through an interaction with RAN
	induces the phosphorylation and nuclear localization of NFKB1
	HSPD1 further activates NLRP3 inflammasome by elevating NLRP3 expression both at RNA and protein levels
	HSPD1 negatively regulates the biological functions of ubiquitin-like protein FAU in macrophages
	HSPD1 might repress CDH1 expression and promote metastatic characters of Buccal mucosa squamous cell carcinoma (BMSCC) cells for poor prognosis of BMSCC patients

cell & other

REGULATION

activated by

MYC (is critical for MYC mediated transformation) (Tsai 2008)

ASSOCIATED DISORDERS

corresponding disease(s)

SPG13 , PMLD2

related resource

MITOP database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in ovarian cancer, pancreatic cancer, large bowel carcinoma (Tsai 2008) tumoral     --low   in clear cell renal cell carcinoma (ccRCC) (pMID: 31112866) tumoral     --low   in hepatocellular carcinoma tissues compared to peritumor tissues tumoral     --over   in glioblastoma patients

Susceptibility

to sudden infant death syndrome (SIDS)

Variant & Polymorphism SNP	pathogenic variant of rs72466451 may play a role in a subgroup of SIDS cases with impaired HSPD1-mediated stress response

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive liver might serve as a potential therapeutic target in the treatment of HCC cancer brain glioma/neuroblstoma is a potential therapeutic target for glioblastoma treatment

ANIMAL & CELL MODELS