HSPA5

HSPA5

heat shock protein family A (Hsp70) member 5 | BiP, GRP78

The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. This protein localizes to the lumen of the endoplasmic reticulum (ER) where it operates as a typical HSP70 chaperone involved in the folding and assembly of proteins in the ER and is a master regulator of ER homeostasis. During cellular stress, as during viral infection or tumorogenesis, this protein interacts with the transmembrane stress sensor proteins PERK (protein kinase R-like endoplasmic reticulum kinase), IRE1 (inositol-requiring kinase 1), and ATF6 (activating transcription factor 6) where it acts as a repressor of the unfolded protein response (UPR) and also plays a role in cellular apoptosis and senescence. Elevated expression and atypical translocation of this protein to the cell surface has been reported in viral infections and some types of cancer cells. At the cell surface this protein may facilitate viral attachment and entry to host cells. This gene is a therapeutic target for the treatment of coronavirus diseases and chemoresistant cancers. [provided by RefSeq, Jul 2020]

Member of: DE-1 DE-1.16 Developmental clusters: GC1

Biological processes 90 terms

ATP binding (GO:0005524)ATP binding (GO:0005524)ATP hydrolysis activity (GO:0016887)ATP hydrolysis activity (GO:0016887)ATP hydrolysis activity (GO:0016887)ATP hydrolysis activity (GO:0016887)COP9 signalosome (GO:0008180)ERAD pathway (GO:0036503)ERAD pathway (GO:0036503)IRE1-mediated unfolded protein response (GO:0036498)cadherin binding (GO:0045296)calcium ion binding (GO:0005509)cell surface (GO:0009986)cellular response to glucose starvation (GO:0042149)cerebellar Purkinje cell layer development (GO:0021680)cerebellum structural organization (GO:0021589)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytosol (GO:0005829)endoplasmic reticulum (GO:0005783)endoplasmic reticulum (GO:0005783)endoplasmic reticulum (GO:0005783)endoplasmic reticulum (GO:0005783)endoplasmic reticulum chaperone complex (GO:0034663)endoplasmic reticulum chaperone complex (GO:0034663)endoplasmic reticulum chaperone complex (GO:0034663)endoplasmic reticulum lumen (GO:0005788)endoplasmic reticulum lumen (GO:0005788)endoplasmic reticulum lumen (GO:0005788)endoplasmic reticulum lumen (GO:0005788)endoplasmic reticulum lumen (GO:0005788)endoplasmic reticulum membrane (GO:0005789)endoplasmic reticulum membrane (GO:0005789)endoplasmic reticulum membrane (GO:0005789)endoplasmic reticulum unfolded protein response (GO:0030968)endoplasmic reticulum unfolded protein response (GO:0030968)endoplasmic reticulum unfolded protein response (GO:0030968)endoplasmic reticulum-Golgi intermediate compartment (GO:0005793)endoplasmic reticulum-Golgi intermediate compartment (GO:0005793)enzyme binding (GO:0019899)enzyme binding (GO:0019899)extracellular exosome (GO:0070062)focal adhesion (GO:0005925)heat shock protein binding (GO:0031072)intracellular membrane-bounded organelle (GO:0043231)maintenance of protein localization in endoplasmic reticulum (GO:0035437)melanosome (GO:0042470)membrane (GO:0016020)membrane (GO:0016020)midbody (GO:0030496)misfolded protein binding (GO:0051787)misfolded protein binding (GO:0051787)mitochondrion (GO:0005739)negative regulation of IRE1-mediated unfolded protein response (GO:1903895)negative regulation of PERK-mediated unfolded protein response (GO:1903898)negative regulation of apoptotic process (GO:0043066)negative regulation of apoptotic process (GO:0043066)negative regulation of protein-containing complex assembly (GO:0031333)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)plasma membrane (GO:0005886)positive regulation of cell migration (GO:0030335)positive regulation of protein catabolic process (GO:0045732)positive regulation of protein ubiquitination (GO:0031398)positive regulation of transcription by RNA polymerase II (GO:0045944)post-translational protein targeting to membrane, translocation (GO:0031204)protein binding (GO:0005515)protein domain specific binding (GO:0019904)protein folding chaperone (GO:0044183)protein folding chaperone (GO:0044183)protein folding chaperone (GO:0044183)protein folding in endoplasmic reticulum (GO:0034975)protein refolding (GO:0042026)protein sequestering activity (GO:0140311)protein serine/threonine kinase inhibitor activity (GO:0030291)protein-containing complex (GO:0032991)protein-folding chaperone binding (GO:0051087)regulation of ATF6-mediated unfolded protein response (GO:1903891)regulation of IRE1-mediated unfolded protein response (GO:1903894)regulation of IRE1-mediated unfolded protein response (GO:1903894)regulation of PERK-mediated unfolded protein response (GO:1903897)regulation of protein folding in endoplasmic reticulum (GO:0060904)response to endoplasmic reticulum stress (GO:0034976)ribosome binding (GO:0043022)substantia nigra development (GO:0021762)ubiquitin protein ligase binding (GO:0031625)unfolded protein binding (GO:0051082)unfolded protein binding (GO:0051082)

Expression (TPM)

TFs regulating HSPA5 0 TFs

Transcription factors with Perturb-seq knockdown data for HSPA5. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = HSPA5 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

TF	Mean coef	Binding	Outlier	TF→Gene link

Rows:

Elements linked to HSPA5

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of HSPA5, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility	Element	Dist. to TSS	Link type	TFs
	chr9:124,940,496–124,941,902	300.3 kb	Distal (>10kb) Multiome	979
	chr9:125,142,890–125,144,084	97.7 kb	Distal (>10kb) Multiome	723
	chr9:125,189,173–125,190,290	51.5 kb	Distal (>10kb) Multiome	830
	chr9:125,199,947–125,201,039	40.8 kb	Distal (>10kb) Multiome	866
	chr9:125,240,934–125,242,115	153 bp	At TSS Multiome	974
	chr9:125,261,500–125,262,311	20.4 kb	Distal (>10kb) Multiome	900
	chr9:125,407,852–125,408,856	166.9 kb	Distal (>10kb) Multiome	615
	chr9:125,515,099–125,515,938	274.1 kb	Distal (>10kb) Multiome	114

Genome Browser

Genomic view of the HSPA5 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.