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FLASH GENE

Symbol

HSP90B1

contributors: mct/pg - updated : 16-03-2016

HGNC name	heat shock protein 90kDa beta (Grp94), member 1
HGNC id	12028

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003299 18 - 2780 NP_003290 100 803 - 2007 17411420 also called HSP90B1-1 variant 2 - - 1381 isoform 2 33 294 lung 2005 16269234 also called HSP90B1-2 variant 3 - - 2349 isoform 3 90 782 liver tumor 2005 16269234 also called HSP90B1-3 variant 5 - - 2824 isoform 5 90 781 in hepatoma 2005 16269234 also called HSP90B1-4

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 blood / hematopoietic spleen       highly Digestive liver       highly Respiratory lung       highly

tissue

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

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 with a nucleotide binding site, a peptide binding site and unmapped sites responsible for interaction with dendritic cells during antigen presentation but not containing the essential protein-binding domain
	a second domain, as in HSP90, that is a charged linker between the N and middle (M) domains, but it is longer in all GRP94s and functionally important for binding of both nucleotide and calcium
	the middle domain interacts with the N-terminal domain
	the C-terminal domain mediates its dimerization and ER localization via the C-terminal KDEL peptide

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine Tra1

intraspecies

paralog to HSP90

Homologene

FAMILY

heat shock protein 90 family

CATEGORY

chaperone/stress , antigen

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,microsome
	intracellular,nucleus
	intracellular,nuclear envelope
text	major luminal constituent of the endoplasmic reticulum with known high capacity for calcium and a peptide-binding activity

basic FUNCTION	ER chaperone functioning in the processing and transport of secreted proteins
	endoplasmic reticulum molecular chaperone, component of the unfolded protein response (UPR), and is involved in apoptosis
	has essential functions in embryonic development
	essential for mesoderm induction and muscle development because it regulates insulin-like growth factor secretion
	having an ATPase activity essential for chaperone activity
	playing an important role for cellular Ca2+ storage
	optimizes the function of B cells by chaperoning TLRs and integrins but not immunoglobulin
	with UNC93B1, and CNPY3, play a role in TLR localisation
	essential for the expression of specific integrins and to selectively regulate early T and B lymphopoiesis
	is a novel cell intrinsic factor required to maintain the interaction of HSCs with their niche, and thus regulate their physiology
	protein expressions of both HSP90B1 and HSPA5 are known to be induced by glucose deprivation
	plays a role as an endogenous TLR2 ligand in rheumatoid arthritis (RA)
	HSP90AA1 and HSP90B1 play key roles in controlling KCNQ4 homeostasis via the HSP40-HSP70-HOP-HSP90 chaperone pathway and the ubiquitin-proteasome pathway
	novel and unique roles in regulating hematopoietic stem cells proliferation
	essential role in regulating melanogenesis
	chaperone function of the ER-residing HSPB1 plays an important role in protein physiology and has additionally important immunological functions due to its peptide-binding capacity
	master TLR and integrin chaperone
	regulates multiple facets of Treg biology, thereby placing Treg stability and immunosuppressive functions strategically under the control of a major stress chaperone

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

homodimer disulfide-linked

INTERACTION

DNA

RNA

small molecule

protein	HSPA9B
	chaperone binding antigenic peptides, to receptors on professional antigen-presenting cells (APCs), activating these cells and after internalization, transfering the peptides to MHC class I for activation of T cells
	associated with OS9
	can form a molecular complex with AIMP1, that regulate the ER retention of HSP90B1 through KDELR1, and suppress its cell surface expression
	HSP90B1 directly interacts with CNPY3, and the complex dissociates in the presence of adenosine triphosphate (ATP)
	CSNK2A1 did phosphorylate HSP90B1 even without the NLS-peptide, suggesting that an additional suppressive factor is required for NLS-dependent phosphorylation of HSP90B1 by CSNK2A1
	is critical for both TLR9 egress from the ER, and for protein conformational stability in the endosomal compartmen
	MZB1 associates directly with the substrate-specific chaperone HSP90B1 in an ATP-sensitive manner and is required for the interaction of HSP90B1 with immunoglobulin heavy chain upon ER stress
	serves as an essential chaperone for the cell-surface protein glycoprotein A repetitions predominant (CD109), which is a docking receptor for latent membrane-associated TGFB1
	HSP90B1 interacts with both TP53 and MDM2 to enhance MDM2-mediated TP53 ubiquitination and degradation
	binding of PCSK9 to HSP90B1 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER
	FKBP8 and HSP90B1 play an essential role in the late phase of CLCN1 quality control by dynamically coordinating protein folding and degradation

cell & other

REGULATION

Other	regulated by adenosine nucleotides that bind to its N-terminal regulatory domain
	regulated by calcium (regulates the ability of HSP90B1 to bind peptides)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   significantly elevated in intestinal biopsies of Crohn disease (CD)which correlated positively with the degree of inflammation of the tissue

Susceptibility

to bipolar disorder

Variant & Polymorphism SNP	associated with bipolar disorder in a Japanese population

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive liver targeting HSP90B1 with siRNA induced cell apoptosis and led to the suppression of liver tumor growth immunology autoimmune   potential new therapeutic target in autoimmune diseases

ANIMAL & CELL MODELS

grp94-/- embryos die on day 7 of gestation, fail to develop mesoderm, primitive streak, or proamniotic cavity